The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/8/705/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 5, August 29, 1997 705-717

Article

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

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

From the * Department of Medicine, {ddagger} 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.

Address correspondence to Dr. Patrick M. Flood, Department of Microbiology and Immunology, Curriculum in Oral Biology, Dental Research Center, University of North Carolina, Chapel Hill, NC 27599-7455. Phone: 919-966-1538; FAX: 919-966-3683; E-mail: patflood{at}dentistry.unc.edu. W.L. Stanford's present address is Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada.

1 Abbreviations used in this paper: Con A, Concanavalin A; ES, embryonic stem; GANC, gancyclovir; GPI, glycosyl phosphatidylinositol; SSLP, simple sequence length polymorphism.


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