Altered proliferative response by T lymphocytes of Ly-6A (Sca-1) null mice

WL Stanford, S Haque, R Alexander, X Liu… - The Journal of …, 1997 - rupress.org
WL Stanford, S Haque, R Alexander, X Liu, AM Latour, HR Snodgrass, BH Koller, PM Flood
The Journal of experimental medicine, 1997rupress.org
Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be involved
in activation of hematopoietic stem cells. Antibody 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-6A null mice which
are healthy and have normal numbers and percentages of hematopoietic lineages.
However, T lymphocytes from Ly-6A–deficient animals proliferate at a significantly higher …
Ly-6A is a murine antigen which is implicated in lymphocyte activation and may be involved in activation of hematopoietic stem cells. Antibody 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-6A null mice which are healthy and have normal numbers and percentages of hematopoietic lineages. However, T lymphocytes from Ly-6A–deficient animals proliferate at a significantly higher rate in response to antigens and mitogens than wild-type littermates. In addition, Ly-6A mutant splenocytes generate more cytotoxic T lymphocytes compared to wild-type splenocytes when cocultured with alloantigen. This enhanced proliferation is not due to alterations in kinetics of response, sensitivity to stimulant 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 to downmodulate lymphocyte responses.
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