Abstract

The contact hypersensitivity reaction (CHS) to haptens is a classic example of cell-mediated immune response. In the effector phase, two stages can be distinguished: an early component, that appears only 2 hours after subsequent contact with the hapten, and the late component that develops approximately 24 hours later which is mediated by TCRαβ+ cells. The effector lymphocytes may be CD4+ T helper 1 (Th1) cells or CD8+ T cytotoxic 1 (Tc1) cells, which depends on the employed hapten and/or mice strain. NKT lymphocytes play the crucial role in the CHS initiation, by supporting B1 cells in the antigen-specific IgM antibodies production. The development of an early component is essential for the recruitment of T effector (Teff) cells to the side of hapten deposition and for the complete expansion of inflammatory reaction. The CHS reaction is under T regulatory (Treg) cells control, both in the induction phase as well as in the effector phase. A new view of a negative regulation of the Tc1 mediated CHS response is based on the suppression induced by epicutaneous (EC) application of protein antigen. The DNP-BSA skin application, on a gauze patch, leads to a state of immunosuppression. This maneuver results in rising the population of Treg cells with TCRαβ+CD4+CD25+Foxp3+ phenotype. The mechanism of suppression requires direct contact between Treg cells and Teff cells and the participation of CTLA-4 molecule is also necessary. The described method of evoking immune tolerance via EC immunization may contribute to elaborate a new method of allergic contact dermatitis therapy. This is because of its effectiveness, ease of induction and non-invasive protein antigen application.

References

• 1. Abe M., Kondo T., Xu H., Fairchild R.L.: Interferon-γ inducible protein(IP-10) expression is mediated by CD8+ T cells and is regulatedby CD4+ T cells during the elicitation of contact hypersensitivity. J.Invest. Dermatol., 1996; 107: 360-366
  Google Scholar
• 2. Adema G.J., Hartgers F., Verstraten R., de Vries E., Marland G.,Menon S., Foster J., Xu Y., Nooyen P., McClanahan T., Bacon K.B., FigdorC.G.: A dendritic-cell-derived C-C chemokine that preferentiallyattracts naïve T cells. Nature, 1997; 387: 713-717
  Google Scholar
• 3. Akiba H., Kehren J., Ducluzeau M.T., Krasteva M., Horand F., KaiserlianD., Kaneko F., Nicolas J.F.: Skin inflammation during contact hypersensitivityis mediated by early recruitment of CD8+ T cytotoxic 1 cellsinducing keratinocyte apoptosis. J. Immunol., 2002; 168: 3079-3087
  Google Scholar
• 4. Anderson C., Hehr A., Robbins R., Hasan R., Athar M., MukhtarH., Elmets C.A.: Metabolic requirements for induction of contacthypersensitivity to immunotoxic polyaromatic hydrocarbons. J.Immunol., 1995; 155: 3530-3537
  Google Scholar
• 5. Antonopoulos C., Cumberbatch M., Mee J.B., Dearman R., Wei X.Q.,Liew F.Y., Kimber I., Groves R.W.: IL-18 is a key proximal mediatorof contact hypersensitivity and allergen-induced Langerhans cellmigration in murine epidermis. J. Leukoc. Biol., 2008; 83: 361-367
  Google Scholar
• 6. Asherson G.L., Ptak W.: Contact and delayed hypersensitivity inthe mouse. I. Active sensitization and passive transfer. Immunol.,1968; 15: 405-416
  Google Scholar
• 7. Askenase P.W.: Yes T cells, but three different T cells (αβ, γδ andNK T cells) and also B-1 cells mediate contact sensitivity. Clin. Exp.Immunol., 2001; 125: 345-350
  Google Scholar
• 8. Askenase P.W., Majewska-Szczepanik M., Kerfoot S., SzczepanikM.: Participation of iNKT cells in the early and late components ofTc1 mediated DNFB contact sensiticity: cooperative role of γδ-T cells.Scand. J. Immunol., 2011; 73: 465-477
  Google Scholar
• 9. Askenase P.W., Szczepanik M., Itakura A., Kiener C., Campos R.A.:Extravascular T-cell recruitment requires initiation begun by Vα14+NKT cells and B-1 B cells. Trends Immunol., 2004; 25: 441-449
  Google Scholar
• 10. Basketter D., Dooms-Goossens A., Karlberg A.T., LepoittevinJ.P.: The chemistry of contact allergy: why is a molecule allergenic?Contact Dermatitis, 1995; 32: 65-73
  Google Scholar
• 11. Berard F., Marty J.P., Nicolas J.F.: Allergen penetration throughthe skin. Eur. J. Dermatol., 2003; 13: 324-330
  Google Scholar
• 12. Biedermann T., Kneilling M., Mailhammer R., Maier K, SanderC.A., Kollias G., Kunkel S.L., Hültner L., Röcken M.: Mast cells controlneutrophil recruitment during T cell-mediated delayed-type hypersensitivityreactions through tumor necrosis factor and macrophageinflammatory protein 2. J. Exp. Med., 2000; 192: 1441-1452
  Google Scholar
• 13. Bouloc A., Cavani A., Katz S.I.: Contact hypersensitivity in MHCclass II-deficient mice depends on CD8 T lymphocytes primed by immunostimulatingLangerhans cells. J. Invest. Dermatol., 1998; 111:44-49
  Google Scholar
• 14. Bour H., Peyron E., Gaucherand M., Garrigue J.L., Desvignes C.,Kaiserlian D., Revillard J.P., Nicolas J.F.: Major histocompatibilitycomplex class I-restricted CD8+ T cells and class II-restricted CD4+T cells, respectively, mediate and regulate contact sensitivity to dinitrofluorobezene.Eur. J. Immunol., 1995; 25: 3006-3010
  Google Scholar
• 15. Campbell J.J., Haraldsen G., Pan J., Rottman J., Qin S., Ponath P.,Andrew D.P., Warnke R., Ruffing N., Kassam N., Wu L., Butcher E.C.:The chemokine receptor CCR4 in vascular recognition by cutaneousbut not intestinal memory T cells. Nature, 1999; 400: 776-780
  Google Scholar
• 16. Campos R.A., Szczepanik M., Itakura A., Akahira-Azuma M.,Sidobre S., Kronenberg M., Askenase P.W.: Cutaneous immunizationrapidly activates liver invariant Vα14 NKT cells stimulating B-1 Bcells to initiate T cell recruitment for elicitation of contact sensitivity.J. Exp. Med., 2003; 198: 1785-1796
  Google Scholar
• 17. Campos R.A., Szczepanik M., Ikatura A., Lisbonne M., Dey N.,Leite-de-Moraes M.C., Askenase P.W.: Interleukin-4-dependent innatecollaboration between iNKT cells and B-1 B cells controls adaptativecontact sensitivity. Immunology, 2006; 117: 536-547
  Google Scholar
• 18. Cavani A., Albanesi C., Traidl C., Sebastiani S., Girolomoni G.: Effectorand regulatory T cells in allergic contact dermatitis. TrendsImmunol., 2001; 22: 118-120
  Google Scholar
• 19. Cavani A., Mei D., Guerra E., Corinti S., Giani M., Pirrotta L.,Puddu P., Girolomoni G.: Patients with allergic contact dermatitis tonickel and nonallergic individuals display different nickel-specific Tcell response. Evidence for the presence of effector CD8+ and regulatoryCD4+ T cells. J. Invest. Dermatol., 1998; 111: 621-628
  Google Scholar
• 20. Cavani A., Nasorri F., Prezzi C., Sebastiani S., Albanesi C., GirolomoniG.: Human CD4+ T lymphocytes with remarkable regulatoryfunctions on dendritic cells and Nickel-specific Th1 immuneresponses. J. Invest. Dermatol., 2000; 114: 295-302
  Google Scholar
• 21. Cella M., Sallusto F., Lanzavecchia A.: Origin, maturation andantigen presenting function of dendritic cells. Curr. Opin. Immunol.,1997; 9: 10-16
  Google Scholar
• 22. Chomiczewska D., Trznadel-Budźko E., Kaczorowska A., RotsztejnH.: Znaczenie komórek Langerhansa w układzie immunologicznymskóry. Pol. Merk. Lekarski, 2009; 26: 173-177
  Google Scholar
• 23. Corsini E., Galli C.L.: Epidermal cytokines in experimental contactdermatitis. Toxicology, 2000; 142: 203-211
  Google Scholar
• 24. Cumberbatch M., Dearman R.J., Griffiths C.E., Kimber I.: EpidermalLangerhans cell migration and sensitization to chemical allergens.APMIS, 2003; 111: 797-804
  Google Scholar
• 25. Cumberbatch M., Dearman R.J., Kimber I.: Langerhans cells requiresignals from both tumor necrosis factor-α and interleukin-1βfor migration. Immunology, 1997; 92: 388-395
  Google Scholar
• 26. Desvignes C., Etchart N., Kehren J., Akiba I., Nicolas J.F., KaiserlianD.: Oral administration of hapten inhibits in vivo inductionof specific cytotoxic CD8+ T cells mediating tissue inflammation:a role for regulatory CD4+ T cells. J. Immunol., 2000; 164: 2515-2522
  Google Scholar
• 27. Dey N., Szczepanik M., Lau K., Majewska-Szczepanik M., AskenaseP.W.: Stimulatory lipids accumulate in the mouse liver within 30min of contact sensitization to facilitate the activation of naïve iNKTcells in a CD1d-dependent fashion. Scand. J. Immunol., 2011, 74: 52-61
  Google Scholar
• 28. Diepgen T.L., Weisshaar E.: Contact dermatitis: epidemiology andfrequent sensitizers to cosmetics. J. Eur. Acad. Dermatol. Venereol.,2007; 21: (Suppl. 2): 9-13
  Google Scholar
• 29. Dubois B., Chapat L., Goubier A., Kaiserlian D.: CD4+CD25+ Tcells as key regulators of immune responses. Eur. J. Dermatol., 2003;13: 111-116
  Google Scholar
• 30. Engeman T., Gorbachev A.V., Kish D.D., Fairchild R.L.: The intensityof neutrophil infiltration controls the number of antigen-primedCD8 T cells recruited into cutaneous antigen challenge sites. J.Leukoc. Biol., 2004; 76: 941-949
  Google Scholar
• 31. Enk A.H., Katz S.I.: Early events in the induction phase of contactsensitivity. J. Invest. Dermatol., 1992; 99: 39S-41S
  Google Scholar
• 32. Enk A.H., Katz S.I.: Early molecular events in the induction phaseof contact sensitivity. Proc. Natl. Acad. Sci. USA, 1992; 89: 1398-1402
  Google Scholar
• 33. Faria A.M., Weiner H.L.: Oral tolerance. Immunol. Rev., 2005;206: 232-259
  Google Scholar
• 34. Ferguson T.A., Dube P., Griffith T.S.: Regulation of contact hypersensitivityby interleukin 10. J. Exp. Med., 1994; 179: 1597-1604
  Google Scholar
• 35. Foussat A., Cottrez F., Brun V., Fournier N., Breittmayer J.P.,Groux H.: A comparative study between T regulatory type 1 andCD4+CD25+ T cells in the control of inflammation. J. Immunol., 2003;171: 5018-5026
  Google Scholar
• 36. Gamerdinger K., Moulon C., Karp D.R., van Bergen J., Koning F.,Wild D., Pflugfelder U., Weltzien H.U.: A new type of metal recognitionby human T cells: contact residues for peptide-independentbridging of T cell receptor and major histocompatibility complexby nickel. J. Exp. Med., 2003; 197: 1345-1353
  Google Scholar
• 37. Geba G.P., Ptak W., Anderson G.M., Paliwal V., Ratzlaff R.E., LevinJ., Askenase P.W.: Delayed-type hypersensitivity in mast cell–deficientmice. Dependence on platelets for expression of contact sensitivity.J. Immunol., 1996; 157: 557-565
  Google Scholar
• 38. Gocinski B.L., Tigelaar R.E.: Roles of CD4+ and CD8+ T cells inmurine contact sensitivity revealed by in vivo monoclonal antibodydepletion. J. Immunol., 1990; 144: 4121-4128
  Google Scholar
• 39. Gorbachev A.V., Dilulio N.A., Fairchild R.L.: IL-12 augments CD8+T cell development for contact hypersensitivity responses and circumventsanti-CD154 antibody-mediated inhibition. J. Immunol.,2001; 167: 156-162
  Google Scholar
• 40. Gorbachev A.V., Fairchild R.L.: CD4+ T cells regulate CD8+ T cell–mediated cutaneous immune responses by restricting effector Tcell development through a Fas ligand-dependent mechanism. J.Immunol., 2004; 172: 2286-2295
  Google Scholar
• 41. Gorbachev A.V., Fairchild R.L.: CD4+CD25+ regulatory T cells utilizeFasL as mechanism to restrict DC priming functions in cutaneousimmune responses. Eur. J. Immunol., 2010; 40: 2006-2015
  Google Scholar
• 42. Gorbachev A.V., Fairchild R.L.: Regulatory role of CD4+ T cellsduring the development of contact hypersensitivity responses. Immunol.Res., 2001; 24: 69-77
  Google Scholar
• 43. Gorbachev A.V., Heeger P.S., Fairchild R.L.: CD4+ and CD8+ T cellpriming for contact hypersensitivity occurs independently of CD40–CD154 interactions. J. Immunol., 2001; 166: 2323-2332
  Google Scholar
• 44. Grabbe S., Schwarz T.: Immunoregulatory mechanisms involvedin elicitation of allergic contact hypersensitivity. Immunol. Today,1998; 19: 37-44
  Google Scholar
• 45. Griffiths C.E., Dearman R.J., Cumberbatch M., Kimber I.: Cytokinesand Langerhans cell mobilization in mouse and man. Cytokine,2005; 32: 67-70
  Google Scholar
• 46. Hauser C.: Cultured epidermal Langerhans cells activate effectorT cells for contact sensitivity. J. Invest. Dermatol., 1990; 95: 436-440
  Google Scholar
• 47. He D., Wu L., Kim H.K., Li H., Elmets C.A., Xu H.: IL-17 and IFN-γmediate the elicitation of contact hypersensitivity responses by differentmechanisms and both are required for optimal responses. J.Immunol., 2009; 183: 1463-1470
  Google Scholar
• 48. Herrick C.A., MacLeod H., Glusac E., Tigelaar R.E., BottomlyK.: Th2 responses induced by epicutaneous or inhalational proteinexposure are differentially dependent on IL-4. J. Clin. Invest., 2000;105: 765-775
  Google Scholar
• 49. Hertl M., Bohlen H., Jugert F., Boecker C., Knaup R., Merk H.F.:Predominance of epidermal CD8+ T lymphocytes in bullous cutaneousreactions caused by β-lactam antibiotics. J. Invest. Dermatol.,1993; 101: 794-799
  Google Scholar
• 50. Herzog W.R., Millet I., Ferreri N.R., Ramabhadran R., Schreurs J.,Askenase P.W.: An antigen-specific DTH-initiating cell clone: functional,phenotypical and partial molecular characterization. J. Immunol.,1990; 144: 3667-3676
  Google Scholar
• 51. Ishii N., Takahashi K., Nakajima H., Tanaka S., Askenase P.W.:DNFB contact sensitivity (CS) in BALB/c and H3H/He mice: requirementfor early-occuring, early-acting, antigen-specific, CS-initiatingcells with an unusual phenotype (Thy-1+, CD5+, CD3-, CD4-, CD8-, sIg-, B220+, MHC class II-, CD23+, IL-2R-, IL-3R+, Mel-14-, Pgp-1+, J11d+,MAC-1+, LFA-1+, and FcγRII+). J. Invest. Dermatol., 1994; 102: 321-327
  Google Scholar
• 52. Itakura A., Szczepanik M., Campos R.A., Paliwal V., MajewskaM., Matsuda H., Takatsu K., Askenase P.W.: An hour after immunizationperitoneal B-1 cells are activated to migrate to lymphoid organswhere within 1 day they produce IgM antibodies that initiateelicitation of contact sensitivity. J. Immunol., 2005; 175: 7170-7178
  Google Scholar
• 53. Juryńczyk M., Walczak A., Jurewicz A., Jesionek-Kupnicka D.,Szczepanik M., Selmaj K.: Immune regulation of multiple sclerosisby transdermally applied myelin peptides. Ann. Neurol., 2010;68: 593-601
  Google Scholar
• 54. Kalish R.S., Askenase P.W.: Molecular mechanisms of CD8+ T cellmediateddelayed hypersensitivity: implications for allergies, asthma,and autoimmunity. J. Allergy Clin. Immunol., 1999; 103: 192-199
  Google Scholar
• 55. Kalish R.S., Wood J.A., LaPorte A.: Processing of urushiol (poisonivy) hapten by both endogenous and exogenous pathways forpresentation to T cells in vitro. J. Clin. Invest., 1994; 93: 2039-2047
  Google Scholar
• 56. Kaplan D.H., Igyártó B.Z., Gaspari A.A.: Early immune enventsin the induction of allergic contact dermatitis. Nat. Rev. Immunol.,2012; 12: 114-124
  Google Scholar
• 57. Kehren J., Desvignes C., Krasteva M., Ducluzeau M.T., AssossouO., Horand F., Hahne M, Kagi D., Kaiserlian D., Nicolas J.F.: Cytotoxicityis mandatory for CD8+ T cell-mediated contact hypersensitivity.J. Exp. Med., 1999; 189: 779-786
  Google Scholar
• 58. Kimber I., Basketter D.A., Gerberick G.F., Dearman R.J.: Allergiccontact dermatitis. Int. Immunopharmacol., 2002; 2: 201-211
  Google Scholar
• 59. Kimber I., Dearman R.J.: Allergic contact dermatitis: the cellulareffectors. Contact Dermatitis, 2002; 46: 1-5
  Google Scholar
• 60. Kish D.D., Gorbachev A.V., Fairchild R.L.: CD8+ T cells produceIL-2, which is required for CD4+CD25+ T cell regulation of effectorCD8+ T cell development for contact hypersensitivity responses. J.Leukoc. Biol., 2005; 78: 725-735
  Google Scholar
• 61. Kish D.D., Gorbachev A.V., Fairchild R.L.: Regulatory function ofCD4+CD25+ T cells from class II MHC-deficient mice in contact hypersensitivityresponses. J. Leukoc. Biol., 2007; 82: 85-92
  Google Scholar
• 62. Kobayashi Y., Matsumoto M., Kotani M., Makino T.: Possible involvementof matrix metalloproteinase-9 in Langerhans cell migrationand maturation. J. Immunol., 1999; 163: 5989-5993
  Google Scholar
• 63. Kolesaric A., Stingl G., Elbe-Bürger A.: MHC class I+/II – dendriticcells induce hapten-specific immune responses in vitro and in vivo.J. Invest. Dermatol., 1997; 109: 580-585
  Google Scholar
• 64. Krasteva M., Kehren J., Ducluzeau M.T., Sayag M., CacciapuotiM., Akiba H., Descotes J., Nicolas J.F.: Contact dermatitis I. Pathophysiologyof contact sensitivity. Eur. J. Dermatol., 1999; 9: 65-77
  Google Scholar
• 65. Krasteva M., Kehren J., Ducluzeau M.T., Sayag M., Dupuis M.,Kanitakis J., Nicolas J.F.: Contact dermatitis II. Clinical aspects anddiagnosis. Eur. J. Dermatol., 1999; 9: 144-160
  Google Scholar
• 66. Krasteva M., Kehren J., Horand F., Akiba H., Choquet G., DucluzeauM.T., Tédone R., Garrigue J.L., Kaiserlian D., Nicolas J.F.:Dual role of dendritic cells in the induction and down-regulationof antigen-specific cutaneous inflammation. J. Immunol., 1998; 160:1181-1190
  Google Scholar
• 67. Krause I., Blank M., Shoenfeld Y.: Immunomodulation of experimentalautoimmune diseases via oral tolerance. Crit. Rev. Immunol.,2000; 20: 1-16
  Google Scholar
• 68. Kripke M.L., Munn C.G., Jeevan A., Tang J.M., Bucana C.: Evidencethat cutaneous antigen-presenting cells migrate to regional lymphnodes during contact sensitization. J. Immunol., 1990; 145: 2833-2838
  Google Scholar
• 69. Lappin M.B., Kimber I., Norval M.: The role of dendritic cellsin cutaneous immunity. Arch. Dermatol. Res., 1996; 288: 109-121
  Google Scholar
• 70. Lepoittevin J.P., Leblond I.: Hapten-peptide-T cell receptor interactions:molecular basis for the recognition of haptens by T lymphocytes.Eur. J. Dermatol., 1997; 7: 151-154
  Google Scholar
• 71. Lobo F., Zając K., Majewska M., Zemelka M., Szczepanik M.: Epicutaneousimmunization with protein antigen protects from collageninduced arthritis. J. Immunol., 2006; 176: 115.13
  Google Scholar
• 72. Majewska M., Zając K., Kubera M., Bryniarski K., Ptak M., BastaKaimA., Książek L., Ptak W., Lasoń W., Szczepanik M.: Effect of ovoalbuminon the survival of an H-Y incompatible skin graft in C57BL/6mice. Pharmacol. Rep., 2006; 58: 439-442
  Google Scholar
• 73. Majewska M., Zając K., Srebro Z., Sura P., Książek L., ZemelkaM., Szczepanik M.: Epicutaneous immunization with myelin basicprotein protects from the experimental autoimmune encephalomyelitis.Pharmacol. Rep., 2007; 59: 74-79
  Google Scholar
• 74. Majewska M., Zając K., Srebro Z., Sura P., Książek L., ZemelkaM., Szczepanik M.: Epicutanepus (EC) immunization with myelinbasic protein (MBP) protects from the experimental autoimmuneencephalomyelitis. Eur. J. Immunol., 2008; 33 (Suppl.1): 2.98
  Google Scholar
• 75. Majewska-Szczepanik M., Zemelka-Wiącek M., Ptak W., Wen L.,Szczepanik M.: Epicutaneous immunization with DNP-BSA inducesCD4(+) CD25(+) Treg cells that inhibit Tc1-mediated CS. Immunol.Cell. Biol., 2012, 90: 784-795
  Google Scholar
• 76. Martin S., Lappin M.B., Kohler J., Delattre V., Leicht C., PreckelT., Simon J.C., Weltzien H.U.: Peptide immunization indicates thatCD8+ T cells are the dominant effector cells in trinitrophenylspecificcontact hypersensitivity. J. Invest. Dermatol., 2000; 115:260-266
  Google Scholar
• 77. Martin S.F.: T lymphocyte-mediated immune responses to chemicalhaptens and metal ions: implications for allergic and autoimmunedisease. Int. Arch. Allergy Immunol., 2004; 134: 186-198
  Google Scholar
• 78. Martin S.F., Dudda J.C., Bachtanian E., Lembo A., Liller S., Dürr C.,Heimesaat M.M., Bereswill S., Fejer G., Vassileva R., Jakob T., FreudenbergN., Termeer C.C., Johner C., Galanos C., Freudenberg M.A.:Toll-like receptor and IL-12 signaling control susceptibility to contacthypersensitivity. J. Exp. Med., 2008; 205: 2151-2162
  Google Scholar
• 79. McHale J.F., Harari O.A., Marshall D., Haskard D.O.: Vascularendothelial cell expression of ICAM-1 and VCAM-1 at the onset ofeliciting contact hypersensitivity in mice: evidence for a dominantrole of TNF-α. J. Immunol., 1999; 162: 1648-1655
  Google Scholar
• 80. Min S.Y., Park K.S., Cho M.L., Kang J.W., Cho Y.G., Hwang S.Y.,Park M.J., Yoon C.H., Min J.K., Lee S.H., Park S.H., Kim H.Y.: Antigeninduced,tolerogenic CD11c+,Cd11b+ dendritic cells are abundantin Peyer’s patches during the induction of oral tolerance to typeII collagen and suppress experimental collagen-induced arthritis.Arthritis Rheum., 2006; 54: 887-898
  Google Scholar
• 81. Mosmann T.R., Coffman R.L.: TH1 and TH2 cells: Different patternsof lymphokine secretion lead to different functional properties.Annu. Rev. Immunol., 1989; 7: 145-173
  Google Scholar
• 82. Moulon C., Wild D., Dormoy A., Weltzien H.U.: MHC-dependentand –independent activation of human nickel-specific CD8+ cytotoxicT cells from allergic donors. J. Invest. Dermatol., 1998; 111: 360-366
  Google Scholar
• 83. Nakamura K., Aizawa M.: Studies on the genetic control of picrylchloride contact hypersensitivity reaction in inbred rats. Transplant.Proc., 1981; 13: 1400-1403
  Google Scholar
• 84. O’Leary J.G., Goodarzi M., Drayton D.L., von Andrian U.H.: T-celland B cell-independent adaptive immunity mediated by naturalkiller cells. Nat. Immunol., 2006; 7: 507-516
  Google Scholar
• 85. Ptak W., Askenase P.W.: γδ cells assist αβ T cells in adoptivetransfer of contact sensitivity. J. Immunol., 1992; 149: 3503-3508
  Google Scholar
• 86. Ptak W., Szczepanik M., Bryniarski K., Tutaj M., Ptak M.: Epicutaneousapplication of protein antigens incorporated into cosmeticcream induces antigen-nonspecific unresponsiveness in mice andaffects the cell-mediated immune responses. Int. Arch. Allergy Immunol.,2002; 128: 8-14
  Google Scholar
• 87. Riemann H., Schwarz A., Grabbe S., Aragane Y., Luger T.A., WysockaM., Kubin M., Trinchieri G., Schwarz T.: Neutralization of IL-12 in vivo prevents induction of contact hypersensitivity and induceshapten-specific tolerance. J. Immunol., 1996; 156: 1799-1803
  Google Scholar
• 88. Ring S., Karakhanova S., Johnson T., Enk A.H., Mahnke K.: Gapjunction between regulatory T cells and dendritic cells prevent sensitizationof CD8+ T cells. J. Allergy Clin. Immunol., 2010; 125: 237-246
  Google Scholar
• 89. Ring S., Oliver S.J., Cronstein B.N., Enk A.H., Mahnke K.:CD4+CD25+ regulatory T cells suppress contact hypersensitivity reactionthrough a CD39, adenosine-dependent mechanism. J. AllergyClin. Immunol., 2009; 123: 1287-1296
  Google Scholar
• 90. Ring S., Schäfer S.C., Mahnke K., Lehr H.A., Enk A.H.: CD4+CD25+regulatory T cells suppress contact hypersensitivity reactionsby blocking influx of effector T cells into inflamed tissue. Eur. J.Immunol., 2006; 36: 2981-2992
  Google Scholar
• 91. Robert C., Kupper T.S.: Inflammatory skin diseases, T cells, andimmune surveillance. N. Engl. J. Med., 1999; 341: 1817-1828
  Google Scholar
• 92. Rock K.L.: A new foreign policy: MHC class I molecules monitorthe outside world. Immunol. Today, 1996; 17: 131-137
  Google Scholar
• 93. Saint-Mezard P., Berard F., Dubois B., Kaiserlian D., Nicolas J.F.:The role of CD4+ and CD8+ T cells in contact hypersensitivity andallergic contact dermatitis. Eur. J. Dermatol., 2004; 14: 131-138
  Google Scholar
• 94. Saint-Mezard P., Chavagnac C., Vocanson M., Kehren J., RozièresA., Bosset S., Ionescu M., Dubois B., Kaiserlian D., Nocolas J.F., BerardF.: Deficient contact hypersensitivity reaction in CD4-/ – mice is becauseof impaired hapten-specific CD8+ T cell functions. J. Invest.Dermatol., 2005; 124: 562-569
  Google Scholar
• 95. Saint-Mezard P., Krasteva M., Chavagnac C., Bosset S., Akiba H.,Kehren J., Kanitakis J., Kaiserlian D., Nicolas J.F., Berard F.: Afferentand efferent phases of allergic contact dermatitis (ACD) can be inducedafter a single skin contact with haptens: evidence using a mousemodel of primary ACD. J. Invest. Dermatol., 2003; 120: 641-647
  Google Scholar
• 96. Saint-Mezard P., Rosieres A., Krasteva M., Berard F., Dubois B.,Kaiserlian D., Nicolas J.F.: Allergic contact dermatitis. Eur. J. Dermatol.,2004; 14: 284-295
  Google Scholar
• 97. Sallusto F., Lenig D., Förster R., Lipp M., Lanzavecchia A.: Twosubsets of memory T lymphocytes with distinct homing potentialsand effector function. Nature, 1999; 401: 708-712
  Google Scholar
• 98. Saloga J., Knop J., Kolde G.: Ultrastructural cytochemical visualizationof chromium in the skin of sensitized guinea pigs. Arch.Dermatol. Res., 1988; 280: 214-219
  Google Scholar
• 99. Sinigaglia F.: The molecular basis of metal recognition by T cells.J. Invest. Dermatol., 1994; 102: 398-401
  Google Scholar
• 100. Staines N.A., Derry C.J., Marinova-Mutafchieva L., Ali N., DaviesD.H., Murphy J.J.: Constraints on the efficacy of mucosal tolerance intreatment of human and animal arthritis diseases. Ann. N. Y. Acad.Sci., 2004; 1029: 250-259
  Google Scholar
• 101. Stern R., Kogan G., Jedrzejas M.J., Soltes L.: The many ways tocleave hyaluronan. Biotechnol. Adv., 2007: 25: 537-557
  Google Scholar
• 102. Stoitzner P., Pfaller K., Stössel H., Romani N.: A close-up viewof migrating Langerhans cells in the skin. J. Invest. Dermatol., 2002;118: 117-125
  Google Scholar
• 103. Szczepanik M.: Regulation of contact hypersensitivity responsesby different populations of T suppressor cells. Skin induced toleranceand its clinical implications. Recent Res. Devel. Immunol.,2002; 4: 641-667
  Google Scholar
• 104. Szczepanik M.: Skin induces tolerance and it’s clinical implications.Mod. Asp. Immunobiol., 2002; 2: 265-268
  Google Scholar
• 105. Szczepanik M.: Skin-induced tolerance and its reversal by Toll–like receptor ligands. Arch. Immunol. Ther. Exp., 2007; 55: 161-172
  Google Scholar
• 106. Szczepanik M., Bryniarski K., Tutaj M., Ptak M., SkrzeczyńskaJ., Askenase P.W., Ptak W.: Epicutaneous immunization induces αβTcellreceptor CD4 CD8 double-positive non-specific suppressor T cellsthat inhibit contact sensitivity via transforming growth factor-beta.Immunology, 2005; 115: 42-54
  Google Scholar
• 107. Szczepanik M., Tutaj M., Bryniarski K., Dittel B.N.: Epicutaneouslyinduced TGF-β-dependent tolerance inhibits experimental autoimmuneencephalomyelitis. J. Neuroimmunol., 2005; 164: 105-114
  Google Scholar
• 108. Takeyoshi M., Lida K., Suzuki K., Yamazaki S.: Skin sensitizationpotency of isoeugenol and its dimers evaluated by a non-radioisotopicmodification of the local lymph node assay and guinea pigmaximization test. J. Appl. Toxicol., 2008; 28: 530-534
  Google Scholar
• 109. Toussirot E.A.: Oral tolerance in the treatment of rheumatoidarthritis. Curr. Drug Targets Inflamm. Allergy, 2002; 1: 45-52
  Google Scholar
• 110. Trautmann A., Akdis M., Kleemann D., Altznauer F., Simon H.U.,Graeve T., Noll M., Bröcker E.B., Blaser K., Akdis C.A.: T cell-mediatedFas-induced keratinocyte apoptosis plays a key pathogenetic role ineczematous dermatitis. J. Clin. Invest., 2000; 106: 25-35
  Google Scholar
• 111. Trial J.: Adoptive transfer of early and late delayed-type hypersensitivityreactions mediated by human T cells. Reg. Immunol.,1989; 2: 14-21
  Google Scholar
• 112. Trial J.: Cooperation between early acting delayed-type hypersensitivityT-cells and cultured effector cells in tumor rejection.Cancer Res., 1988; 48: 5922-5926
  Google Scholar
• 113. Tsuji R.F., Geba G.P., Wang Y., Kawamoto K., Matis L.A., AskenaseP.W.: Required early complement activation in contact sensitivitywith generation of local C5-dependent chemotactic activity and lateT cell interferon γ: a possible initiating role of B cell. J. Exp. Med.,1997; 186: 1015-1026
  Google Scholar
• 114. Tsuji R.F., Kawikova I., Ramabhadran R., Akahira-Azuma M.,Taub D., Hugli T.E, Gerard C., Askenase P.W.: Early local generation ofC5a initiates the elicitation of contact sensitivity by leading to earlyT cell recruitment. J. Immunol., 2000; 165: 1588-1598
  Google Scholar
• 115. Tsuji R.F., Kikuchi M., Askenase P.W.: Possible involvement ofC5/C5a in the efferent and elicitation phases of contact sensitivity.J. Immunol., 1996; 156: 4444-4450
  Google Scholar
• 116. Tsuji R.F., Szczepanik M., Kawikova I., Paliwal V., CamposR.A., Itakura A., Akahira-Azuma M., Baumgarth N., HerzenbergL.A., Askenase P.W.: B cell-dependent T cell responses: IgM antibodiesare required to elicit contact sensitivity. J. Exp. Med., 2002;196: 1277-1290
  Google Scholar
• 117. Tutaj M., Szczepanik M.: Epicutaneous (EC) immunization withmyelin basic protein (MBP) induces TCRαβ+ CD4+ CD8+ double positivesuppressor cells that protect from experimental autoimmuneencephalomyelitis (EAE). J. Autoimmunol., 2007; 28: 208-215
  Google Scholar
• 118. Van Beelen A.J., Teunissen M.B., Kapsenberg M.L., Jong E.C.:Interleukin-17 in inflammatory skin disorders. Curr. Opin. AllergyClin. Immunol., 2007; 7: 374-381
  Google Scholar
• 119. Van Hoogstraten I.M., Boden D., von Blomberg M.E., Kraal G.,Scheper R.J.: Persistent immune tolerance to nickel and chromiumby oral administration prior to cutaneous sensitization. J. Invest.Dermatol., 1992; 99: 608-616
  Google Scholar
• 120. Van Hoogstraten I.M., Boos C., Boden D., von Blomberg M.E.,Scheper R.J.: Oral induction of tolerance to nickel sensitization inmice. J. Invest. Dermatol., 1993; 101: 26-31
  Google Scholar
• 121. Van Loveren H., Askenase P.W.: Delayed-type hypersensitivityis mediated by a sequence of two different T cell activities. J. Immunol.,1984; 133: 2397-2401
  Google Scholar
• 122. Vocanson M., Rozieres A., Hennino A., Poyet G., Gaillard V.,Renaudineau S., Achachi A., Benetiere J., Kaiserlian D., Dubois B.,Nicolas J.F.: Inducible costimulator (ICOS) is a marker for highlysuppressive antigen-specific T cells sharing features of Th17/Th1and regulatory T cells. J. Allergy Clin. Immunol., 2010; 126: 280-288
  Google Scholar
• 123. Wagner L., Yang O.O., Garcia-Zepeda E.A., Ge Y., Kalams S.A.,Walker B.D., Pasternack M.S., Luster A.D.: Beta-chemokines are reeased from HIV-1-specific cytolytic T-cell granules complexed toproteoglycans. Nature, 1998; 391: 908-911
  Google Scholar
• 124. Wang B., Esche C., Mamelak A., Freed I., Watanabe H., SauderD.N.: Cytokine knockouts in contact hypersensitivity research. CytokineGrowth Factor Rev., 2003; 14: 381-389
  Google Scholar
• 125. Wang B., Fujisawa H., Zhuang L., Freed I., Howell B.G., ShahidS., Shivji G.M., Mak T.W., Sauder D.N.: CD4+ Th1 and CD8+ type 1cytotoxic T cells both play a crucial role in the full development ofcontact hypersensitivity. J. Immunol., 2000; 165: 6783-6790
  Google Scholar
• 126. Wang B., Fujisawa H., Zhuang L., Kondo S., Shivji G.M., KimC.S., Mak T.W., Sauder D.N.: Depressed Langerhans cell migrationand reduced contact hypersensitivity response in mice lacking TNFreceptor p75. J. Immunol., 1997; 159: 6148-6155
  Google Scholar
• 127. Wang L.F., Wu J.T., Sun C.C.: Local but not systemic administrationof IFN-gamma during the sensitization phase of protein antigenimmunization suppress Th2 development in a murine modelof atopic dermatitis. Cytokine, 2002; 19: 147-152
  Google Scholar
• 128. Watanabe H., Unger M., Tuvel B., Wang B., Sauder D.N.: Contacthypersensitivity: the mechanism of immune responses and T cellbalance. J. Interferon Cytokine Res., 2002; 22: 407-412
  Google Scholar
• 129. Weber F.C., Esser P.R., Müller T., Ganesan J., Pellegatti P., SimonM.M., Zeiser R., Idzko M., Jakob T., Martin S.F.: Lack of the purinergicreceptor P2X7 results in resistance to contact hypersensitivity.J. Exp. Med., 2010: 207: 2609-2619
  Google Scholar
• 130. Weiner H.L.: Oral tolerance, an active immunologic processmediated by multiple mechanisms. J. Clin. Invest., 2000; 106: 935-937
  Google Scholar
• 131. Weiner H.L.: Oral tolerance: immune mechanisms and thegeneration of Th3-type TGF-β-secreting regulatory cells. MicrobesInfect., 2001; 3: 947-954
  Google Scholar
• 132. Weiner H.L., Friedman A., Miller A., Khoury S.J., Al-Sabbagh A.,Santos L., Sayegh M., Nussenblatt R.B., Trentham D.E., Hafler D.A.:Oral tolerance: immunologic mechanisms and treatment of animaland human organ-specific autoimmune diseases by oral administrationof autoantigens. Annu. Rev. Immunol., 1994; 12: 809-837
  Google Scholar
• 133. Weltzien H.U., Moulon C., Martin S., Padovan E., Hartmann U.,Kohler J.: T cell immune response to haptens. Structural models forallergic and autoimmune reactions. Toxicology, 1996; 107: 141-151
  Google Scholar
• 134. Xiao B.G., Link H.: Mucosal tolerance: a two-edged sword toprevent and treat autoimmune diseases. Clin. Immunol. Immuopathol.,1997; 85: 119-128
  Google Scholar
• 135. Xu H., Banerjee A., Dilulio N.A., Fairchild R.L.: Development ofeffector CD8+ T cells in contact hypersensitivity occurs independentlyof CD4+ T cells. J. Immunol., 1997; 158: 4721-4728
  Google Scholar
• 136. Xu H., Dilulio N.A., Fairchild R.L.: T cell populations primedby hapten sensitization on contact sensitivity are distinguishedby  polarized patterns of cytokine production: interferon-γ-producing (Tc1) effector CD8+ T cells and interleukin (IL) 4/IL-10–producing (Th2) negative regulatory CD4+ T cells. J. Exp. Med., 1996;183: 1001-1012
  Google Scholar
• 137. Zając K., Stochmal E., Szczepanik M.: Epicutaneous immunizationwith collagen protects from the development of collageninduced arthritis (CIA). Eur. J. Immunol., 2008; 33 (Suppl. 1): 2.82
  Google Scholar
• 138. Zemelka M., Szczepanik M.: Epicutaneous (ec) immunizationwith DNP-coupled protein antigen suppresses Tc1 CD8+ mediatedcontact sensitivity in mice. Eur. J. Immunol., 2008; 33 (Suppl. 1): 6.96
  Google Scholar
• 139. Zemelka-Wiącek M., Majewska-Szczepanik M., Ptak W., SzczepanikM.: Epicutaneous immunization with protein antigen inducesantigen-non-specific suppression of CD8 T cell mediated contactsensitivity. Pharmacol. Rep., 2012; 64: 1497-1504
  Google Scholar

Full text