title: Epicutaneous immunization with TNP-Ig and Zymosan induces TCRαβ+ CD4+ contrasuppressor cells that reverse skin-induced suppression via IL-17A.
abstract: BACKGROUND
  Our previous work showed that epicutaneous (EC) immunization with protein antigen e.g. TNP-conjugated mouse immunoglobulin (TNP-Ig) in the form of a patch prior to hapten sensitization inhibits Th1-mediated contact hypersensitivity (CHS) in mice. We also found that suppression of CHS was mediated by TCRαβ+ CD4+ CD8+ T suppressor cells producing TGF-β. The aim of this study was to investigate the role of innate immunity in the suppression of CHS.
  
  
  METHODS
  Mice were immunized by applying gauze patches containing protein antigen alone or in the presence of zymosan, and were then tested for the CHS response. Adoptive cell transfer experiments were used to study the mechanisms involved in the reversal of skin-induced suppression. The influence of EC immunization on cytokine production by lymph node cells was measured by ELISA.
  
  
  RESULTS
  We found that EC immunization with TNP-Ig and zymosan before trinitrophenyl chloride sensitization reverses skin-induced suppression, demonstrated in vivo and in vitro. The reversal of skin-induced suppression was transferable by antigen-specific TCRαβ+ CD4+ T contrasuppressor cells. Furthermore, we showed that the contrasuppression was IL-17A-dependent and TLR2- and MyD88-independent.
  
  
  CONCLUSIONS
  Our work strongly suggests that EC immunization with protein antigen and zymosan reverses skin-induced suppression and that this approach may be a potential tool to increase the immunogenicity of weakly immunogenic antigens.
authors.affiliation: Department of Medical Biology, Faculty of Health Sciences, Jagiellonian University College of Medicine, Krakow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Majewska-Szczepanik
authors.forename: Anna
authors.initials: A
authors.lastname: Strzepa
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Marcińska
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000941:Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003877:Dermatitis, Contact / Q000276:immunology; D006241:Haptens / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D007114:Immunization / Q000379:methods; D007136:Immunoglobulins / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods; D020381:Interleukin-17 / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D012867:Skin / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D014301:Trinitrobenzenes / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D015054:Zymosan / Q000276:immunology*
chemical_list: D000941:Antigens; D006241:Haptens; D007136:Immunoglobulins; D020381:Interleukin-17; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D016212:Transforming Growth Factor beta; D014301:Trinitrobenzenes; D015054:Zymosan