Role of the CD5 molecule on TCR gd T cell- mediated immune functions: development of germinal centers and chronic intestinal in ̄ammation

Although CD4+ T cells form a major subset of TCRab T cells, only a small number of TCRgd T cells express CD4. Factors contributing to the down-regulation of CD4+ TCRgd T cells have not been identi®ed. The CD5 molecule is expressed on most TCRgd T cells in the spleen, whereas only a few intestinal intraepithelial TCRgd T cells express this molecule in wild-type mice and TCRb mutant (b±/±) mice. Unexpectedly, in the present studies, the lack of CD5 led to a remarkable increase of a CD4+ TCRgd T cell subset in CD5±/±b±/± mice. The CD4+ TCRgd T cells were also detectable in MHC II±/±CD5±/±b±/± triple-mutant mice. This CD4+ TCRgd T cell subset provided help in Mycobacteriuminduced germinal center (GC) formation and showed a Th-like cytokine pro®le. In contrast, CD5+ TCRgd T cells suppressed the CD4+ TCRgd T cell-mediated GC formation, presumably by eliminating this CD4+ subset. Unlike intraepithelial gd T cells, >30% of TCRgd T cells in the colonic lamina propria (LP) expressed CD5. The lack of CD5 also led to increased numbers of CD4+ TCRgd T cells in the colonic LP and increased susceptibility to development of chronic colitis in b±/± mice. Cell transfer studies suggest that CD5+ TCRgd T cells are capable of selectively eliminating CD4+ TCRgd T cells in the intestine. The CD4+ TCRgd T cells possess immune functions similar to CD4+ TCRab T cells.