Impaired peripheral deletion of activated T cells in mice lacking the common cytokine receptor gamma-chain: defective Fas ligand expression in gamma-chain-deficient mice.
Mice lacking the common cytokine receptor gamma-chain (gamma c) exhibit severely compromised lymphoid development. T cells that develop in these mice exhibit decreased Bcl-2 levels and accelerated apoptosis; nevertheless, these mice exhibit an age-dependent accumulation of activated CD4+ T cells. To investigate the basis for this accumulation, we analyzed both thymic and peripheral deletion in these mice. Gamma c-deficient mice had increased numbers of V beta 11+ T cells, consistent with a possible defect in Mtv-9-induced deletion; however, the deletion of V beta 5+ T cells by Mtv-9 and that of V beta 6+ T cells by Mls-1a were normal. Moreover, antigenic peptide could induce wild-type levels of deletion of CD4+ CD8+ thymocytes in TCR-transgenic gamma c-deficient mice. In contrast to this relatively normal deletion of thymocytes, bacterial superantigen (staphylococcal enterotoxin B)-induced elimination of peripheral T cells was greatly impaired, suggesting that defective peripheral deletion contributed to the accumulation of activated T cells. Interestingly, despite CD4+ T cell accumulation, these cells exhibited increased sensitivity to Fas-mediated death in vitro. Correction of the defect in Bcl-2 expression by mating to Bcl-2 transgenic mice augmented the splenic T cell accumulation and substantially enhanced the survival of gamma c-deficient T cells; however, these cells still exhibited significant Fas-mediated death, indicating that the increased Fas- mediated death was not simply due to diminished Bcl-2 expression. Moreover, these T cells exhibit decreased expression of Fas ligand, suggesting that Fas-bearing cells cannot be effectively eliminated in vivo in gamma c-deficient mice. Thus, gamma c-dependent signals play a role in peripheral T cell deletion, presumably by inducing Fas ligand on activated T cells.[1]References
- Impaired peripheral deletion of activated T cells in mice lacking the common cytokine receptor gamma-chain: defective Fas ligand expression in gamma-chain-deficient mice. Nakajima, H., Leonard, W.J. J. Immunol. (1997) [Pubmed]
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