Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor beta II receptor

The immune system, despite its complexity, is maintained at a relative stea dy state. Mechanisms involved in maintaining lymphocyte homeostasis are poo rly understood; however, recent availability of transgenic (Tg) and knockou t mouse models with altered balance of lymphocyte cell populations suggest that cytokines play a major role in maintaining lymphocyte homeostasis. We show here that transforming growth factor (TGF)-beta plays a critical role in maintaining CD8(+) T cell homeostasis in a Tg mouse model that specifica lly overexpresses a dominant negative TGF-beta II receptor (DNRII) on T cel ls. DNRII T cell Tg mice develop a CD8(+) T cell lymphoproliferative disord er resulting in the massive expansion of the lymphoid organs. These CD8(+) T cells are phenotypically "naive" except for the upregulation of the cell surface molecule CD44, a molecule usually associated with memory T cells. D espite their dominance in the peripheral lymphoid organs, CD8(+) T cells ap pear to develop normally in the thymus, suggesting that TGF-beta exerts its homeostatic control in the peripheral immune system.