Regulatory function of CD4+CD25+ T cells from Class II MHC-deficient mice in contact hypersensitivity responses.
Contact hypersensitivity (CHS) is a CD8+ T cell-mediated, inflammatory response to hapten sensitization and challenge of the skin. During sensitization, the magnitude and duration of hapten-specific CD8+ T cell expansion in the skin-draining lymph nodes (LN) are restricted by CD4+CD25+ T regulatory cells (Treg). The regulation of hapten-specific CD8+ T cell priming in Class II MHC-deficient (MHC-/-) mice was investigated. Although hapten-specific CD8+ T cell priming and CHS responses were elevated in Class II MHC-/- versus wild-type mice, presensitization depletion of CD4+ or CD25+ cells in Class II MHC-/- mice further increased CD8+ T cell priming and the elicited CHS response. Flow cytometry analyses of LN cells from Class II MHC-/- mice revealed a population of CD4+ T cells with a majority expressing CD25. Forkhead box p3 mRNA was expressed in LN cells from Class II MHC-/- and was reduced to background levels by depletion of CD4+ or CD25+ cells. Isolated CD4+CD25+ T cells from wild-type and Class II MHC-/- mice limited in vitro proliferation of alloantigen- and hapten-specific T cells to antigen-presenting stimulator cells. These results identify functional CD4+CD25+ Treg in Class II MHC-/- mice, which restrict hapten-specific CD8+ T cell priming and the magnitude of CHS responses.
Kish
Danielle D
DD
Department of Immunology, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195-0001, USA. kishd@ccf.org
Gorbachev
Anton V
AV
Fairchild
Robert L
RL
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003877:Dermatitis, Contact / Q000276:immunology*; D006241:Haptens / Q000276:immunology; D000949:Histocompatibility Antigens Class II; D008198:Lymph Nodes / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D006241:Haptens; D000949:Histocompatibility Antigens Class II