Contrasting effects of FLIPL overexpression in human T cells on activation-induced cell death and cytokine production

There have been disparate findings about the role of FLIP in the survival of mouse T cells and human tumor cell lines. The role of cellular FLIP in human T cell activation and function needs to be clarified further. To study this role, we have overexpressed long transcript FLIP (FLIPL) in primary T cells, including self-antigen-reactive, melanoma-specific T cells. We found that FLIPL overexpression protects human T cells from activation-induced cell death and enhances their prolifertive capacity but suppresses the ability of these cells to produce the proinflammatory cytokines IL-2 and IFN-gamma in response to CD3 or antigen-specific stimulation. The multiple effects of FLIPL indicate that this protein may influence T cell responses to antigenic stimulation.