Role of the CD5 molecule on TCR γδ T cell-mediated immune functions: Development of germinal centers and chronic intestinal inflammation

Abstract

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