J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/08/705/13 $2.00
Volume 186, Number 5, August 29, 1997 705-717

Altered Proliferative Response by T Lymphocytes of Ly-6A (Sca-1) Null Mice

By William L. Stanford,^* Salma Haque,^¶ Robert Alexander, Xuemei Liu, Anne M. Latour,^* H. Ralph Snodgrass,^** Beverly H. Koller,^* and Patrick M. Flood^§¶

From the ^* Department of Medicine,  Curriculum in Genetics and Molecular Biology, ^§ Department of Microbiology and Immunology,  Curriculum in Oral Biology, and ^¶ Dental Research Center, University of North Carolina, Chapel Hill, North Carolina 27599-7455; and ^** Progenitor, Inc., Columbus, Ohio 43212-1566

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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