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Published online before print February 20, 2007

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(Journal of Leukocyte Biology. 2007;81:1297-1302.)
© 2007 by Society for Leukocyte Biology

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

Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

¹ Correspondence at current address: Max-Delbruck-Center for Molecular Medicine, Robert-Rossle-Strasse 10, 13092, Berlin, Germany. E-mail: j.charo{at}mdc-berlin.de

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 (FLIP_L) in primary T cells, including self-antigen-reactive, melanoma-specific T cells. We found that FLIP_L 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- in response to CD3 or antigen-specific stimulation. The multiple effects of FLIP_L indicate that this protein may influence T cell responses to antigenic stimulation.

Key Words: tumor • autoimmunity • apoptosis • cellular activation • tolerance