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.