Transforming Growth Factor Beta Suppression of CD8+ T Cell Proliferation

Transforming Growth Factor Beta (TGF-beta) is highly suppressive to both CD4+ and CD8+ T cell proliferation and function. in tumor microenvironments, TGF-beta has been described as immune suppressive, particularly to CD8+ T cells, however, the molecular mechanism behind how TGF-beta signaling controls T cell growth is not fully understood. Here, we report that TGF-beta inhibits CD8+ T cell proliferation and reduces expression of the CARMA1/BCL10/MALT1 (CBM) signalosome complex in activated CD8+ T cells. the CBM signalosome is an essential scaffold that forms after T cell receptor (TCR) stimulation, leading to the activation of NF-kB and AP-1. This observed reduction in the CBM complex occurs simultaneously with a reduction in CD25 (IL-2Ralpha) expression. Together, the data suggest that TGF-beta inhibits antigen-stimulated CD8+ T cells by reducing CD25 expression and defines that the CBM complex may be one of the targets that mediates the effects of TGF-beta on CD25 expression