Activated CD4+CD25+ T cells selectively kill B lymphocytes

The suppressive capacity of naturally occurring mouse CD4(+)CD25(+) T cells on T-cell activation has been well documented. The present study is focused on the interaction of CD4(+)CD25(+) T cells and B cells. By coculturing preactivated CD4(+)CD25(+) T cells with B cells in the presence of polyclonal B-cell activators, we found that B-cell proliferation was significantly suppressed. The suppression of B-cell proliferation was due to increased cell death caused by the CD4(+)CD25(+) T cells in a cell-contact-dependent manner. The induction of B-cell death is not mediated by Fas-Fas ligand pathway, but surprisingly, depends on the up-regulation of perforin and granzymes in the CD4(+)CD25(+) T cells. Furthermore, activated CD4(+)CD25(+) T cells preferentially killed antigen-presenting but not bystander B cells. Our results demonstrate that CD4(+)CD25(+) T cells can act directly on B cells and suggest that the prevention of autoimmunity by CD4(+)CD25(+) T cells can be explained, at least in part, by the direct regulation of B-cell function.