Role of the CD5 molecule on TCR [gamma][delta] T cell-mediated immune functions: development of germinal centers and chronic intestinal inflammation

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