Mechanisms of central and peripheral tolerance prevent autoimmunity. Regulatory T cells inhibit the activation of potentially auto-reactive T cells in peripheral lymphoid organs. In transgenic mice in which all MHC class II molecules are incapable of binding to CD4, class II MHC-restricted T cells preferentially differentiated into immunosuppressive, regulatory T cells. In these mutant MHC class II transgenic mice, a subset of CD4(+) T cells constitutively expressed moderately elevated levels of CD25 and potently inhibited interleukin-2 secretion by T cells from normal mice in a cell-to-cell, contact-dependent manner. Immunosuppressive activity depended on activation of the regulatory T cells. Thus, CD25(+)CD4(+) T cells from mutant MHC class II transgenic mice resembled phenotypically and functionally a major subset of natural regulatory T cells in normal mice, but were two to three-times more abundant. These results further clarify the mechanisms that govern the differentiation and maintenance of CD25(+)CD4(+) regulatory T cells, and present avenues for immunomodulation.
Keywords: AICD; APC; Ab; Aging mice; CD25; CD4-MHC class II interactions; CD95; Effector/memory T cells; FITC; IFN; IL-2; Immunosuppression; MHC; Naïve T cells; Ova323; R-PE; Regulatory T cells; SEA; SEB; Staphylococcal enterotoxin A; Staphylococcal enterotoxin B; T cell receptor; TCR; Treg; activation-induced cell death; antibody; antigen-presenting cell; fluorescein isothiothyanate; interferon; interleukin-2; major histocompatibility complex; ovalbumin peptide 323-339; phycoerythrin; regulatory T cells.
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