FUNCTIONAL AND PHENOTYPIC CHANGE OF T-CELLS IN MURINE ACQUIRED IMMUNE-DEFICIENCY

Infection of susceptible C57BL/6 mice with defective LP-BM5 murine leu kemia virus causes disease termed murine acquired immune deficiency sy ndrome (MAIDS). The disease is characterized by lymphoadenopathy, hype rimmunoglobulinemia, and immune deficiency in both T and B cell functi ons. The development of disease requires the presence of mature T cell s, especially CD4 T cells, and B cells. It has previously been shown t hat a B cell tumor line derived from MAIDS mouse stimulated a large fr action of unprimed T cells based on TCR V beta chain expression. This stimulatory activity was assumed to be mediated by a superantigen enco ded by MAIDS virus. The stimulation of T cells by viral superantigen w as thought to play a role in the development of the disease. To examin e the role of T cell reactivity to MAIDS superantigen, we used TCR tra nsgenic mice. There are two distinct T cell populations which can be d istinguished based on their TCR expression and function in the TCR tra nsgenic mice, one bearing the transgene derived alpha- and beta-chain TCR that is nonreactive to MAIDS superantigen and the other bearing an endogenous alpha- but transgene-derived beta-chain TCR that is reacti ve to superantigen. Unlike T cells Found in noninfected TCR transgenic mice, anergic T cells expanding in virally infected TCR transgenic mi ce are homogeneous for the TCR phenotype, indicating the presence of a selection of T cells based on their TCR expression. T cell hybridomas established by fusing T cells from virus-infected transgenic mice to thymoma cell line are also anergic. We found mRNA of defective LP-BM5 virus in a majority of T cell hybridomas from virus-infected mice but not from noninfected mice. By using in vitro infection of T cell clone s with recombinant virus containing LP-BM5 MAIDS virus gag gene, we ha ve demonstrated that virus infection directly abrogated the Ag-specifi c reactivity of T cells. The establishment of anergic T cell hybridoma s and the in vitro infection of T cells with recombinant viruses would be a useful tool in the analysis of biochemical and molecular mechani sms of T cell dysfunction in MAIDS.