Mice infected with a mixture of retroviruses, termed LP-BM5 murine leukemia viruses (MuLV), develop an immunodeficiency and lymphoproliferative syndrome with many similarities to human AIDS. We have investigated cellular interactions that contribute to the development of these abnormalities. One of the central features of this disease is dysfunction of CD4+ T cells. It was shown that in vivo, development of phenotypic and functional abnormalities of this T cell subset is dependent on the presence of mature B cells. In vitro analyses of this phenomenon suggested that several mechanisms may contribute to induction of this abnormality. First, normal CD4+ T cells providing help for self + X cytotoxic T lymphocyte (CTL) responses were found to be actively inhibited by cells from infected mice, suggesting induction of suppressor cells following infection. Second, antigen specific T cell clones were shown to proliferate poorly in response to antigen presented by spleen cells from infected mice suggesting impaired function of antigen presenting cells (APC). Finally, we demonstrated that CD4+ T cells primed in vivo to soluble antigens were impaired in their ability to generate secondary in vitro proliferative responses, suggesting an acquired intrinsic defect of CD4+ cells. In other studies, we have found that an active anti-viral CTL response can be generated in mice susceptible to the disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Intramural Research (Z01)
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