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From the * Department of Medicine, 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.
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
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