title: Epicutaneous immunization with DNP-BSA induces CD4+ CD25+ Treg cells that inhibit Tc1-mediated CS.
abstract: As we have shown previously that protein antigen applied epicutaneously (EC) in mice inhibits TNP-specific Th1-mediated contact sensitivity (CS), we postulated that the maneuver of EC immunization might also suppress Tc1-dependent CS response. Here we showed that EC immunization of normal mice with 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) applied on the skin in the form of a patch induces a state of subsequent unresponsiveness due to regulatory T cells (Treg) that inhibited sensitization and elicitation of effector T-cell responses. Suppression is transferable in vivo by TCRαβ(+) CD4(+) CD25(+) lymphocytes harvested from lymph nodes (LNs) of skin-patched animals. Flow cytometry revealed that EC immunization with DNP-BSA increased TCRαβ(+) CD4(+) CD25(+) FoxP3(+) lymphocytes in subcutaneous LNs, suggesting that observed suppression was mediated by Treg cells. Further, in vitro experiments showed that EC immunization with DNP-BSA prior to 1-fluoro-2,4-dinitrobenzen sensitization suppressed LN cell proliferation and inhibited production of TNF-α, IL-12 and IFN-γ. Using a transwell system or anti-CTLA-4 mAb, we found that EC induced suppression required direct Treg-effector cell contact and is CTLA-4-dependent.
authors.affiliation: Department of Medical Biology, Jagiellonian University College of Medicine, Krakow, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Majewska-Szczepanik
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zemelka-Wiącek
authors.forename: Włodzimierz
authors.initials: W
authors.lastname: Ptak
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D060908:CTLA-4 Antigen / Q000276:immunology; D002450:Cell Communication; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003877:Dermatitis, Contact / Q000150:complications / Q000276:immunology* / Q000473:pathology; D004140:Dinitrophenols / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007114:Immunization; D007249:Inflammation / Q000150:complications / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D060908:CTLA-4 Antigen; D016207:Cytokines; D004140:Dinitrophenols; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D018836:Inflammation Mediators; D053645:Interleukin-2 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; C034638:dinitrophenyl-bovine serum albumin; D012710:Serum Albumin, Bovine