ALTERED PROLIFERATIVE RESPONSE BY T-LYMPHOCYTES OF LY-6A (SCA-1) NULLMICE

Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be involved in activation of hematopoietic stem cells. Antibo dy cross-linking studies and antisense experiments have suggested that Ly-6A is a lymphocyte coactivation molecule. To better understand the function of Ly-6A, we used gene targeting to produce Ly-GA null mice which are healthy and have normal numbers and percentages of hematopoi etic lineages. However, T lymphocytes from Ly-GA-deficient animals pro liferate at a significantly higher rate in response to antigens and mi togens than wild-type littermates. In addition, Ly-6A mutant splenocyt es generate more cytotoxic T lymphocytes compared to wild-type splenoc ytes when cocultured with alloantigen. This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimula nt concentration, or cytokine production by the T cell population, and is manifest in both in vivo and in vitro T cell responses. Moreover, T cells from Ly-6A-deficient animals exhibit a prolonged proliferative response to antigen stimulation, thereby suggesting that Ly-6A acts t o downmodulate lymphocyte responses.