The Role of the Common Cytokine Receptor gamma -Chain in Regulating IL-2-Dependent, Activation-Induced CD8 super(+) T Cell Death

• Published in: The Journal of immunology (1950) Vol. 163; no. 6; pp. 3131 - 3137
• Main Authors: Dai, Z, Arakelov, A, Wagener, M, Konieczny, B T, Lakkis, F G
• Format: Journal Article
• Language: English
• Published: 15.09.1999
• ISSN: 0022-1767

IL-2-dependent, activation-induced T cell death (AICD) plays an important role in peripheral tolerance. Using CD8 super(+) TCR-transgenic lymphocytes (2C), we investigated the mechanisms by which IL-2 prepares CD8 super(+) T cells for AICD. We found that both Fas and TNFR death pathways mediate the AICD of 2C cells. Neutralizing IL-2, IL-2R alpha , or IL-2R beta inhibited AICD. In contrast, blocking the common cytokine receptor gamma -chain ( gamma c) prevented Bcl-2 induction and augmented AICD. IL-2 up-regulated Fas ligand (FasL) and down-regulated gamma c expression on activated 2C cells in vitro and in vivo. Adult IL-2 gene-knockout mice displayed exaggerated gamma c expression on their CD8 super(+), but not on their CD4 super(+), T cells. IL-4, IL-7, and IL-15, which do not promote AICD, did not influence FasL or gamma c expression. These data provide evidence that IL-2 prepares CD8 super(+) T lymphocytes for AICD by at least two mechanisms: 1) by up-regulating a pro-apoptotic molecule, FasL, and 2) by down-regulating a survival molecule, gamma c.