CD4/CD8/ALPHA BETA T CELLS IN AUTOIMMUNE MICE

Stanford University, Stanford CA

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Abstract

Recently our laboratory has developed a new model of murine lupus based on the injection of BALB/c anti-CD1 transgenic T cells into BALB/c nude mice. Host develop anti-DNA antibodies, proteinuria, glomerulonephritis, ascites and anemia. Transgenic CD4+ and CD8+ Tcells induce the disease, and transgenic CD4- CD8- T cells recognize the CD1 molecule on the surface of subsets of B cells, and polyclonally activate the latter cells to secrete lgG and pathogenic autoantibodies. We theorize that the anti-CD1-inducing T cells also help B cells to make antibody responses to polysaccaride antigens such as SSIII and alpha 1,3 dextran via interaction with the CD1 molecule (itself or as antigen presenting molecule for sugar residues). The suppressing transgenic T cells are theorized to inhibit their responses. In order to test the hypothesis, inducing and suppressing purified transgenic T cells will be added to B cell sources in vitro to assay for the secretion oflgG and anti-DNA antibodies in vitro. In similar studies, the ability of these anti-CD1 T cells to regulate the in vitro and in vivo polysaccharide antibody responses will be examined. ELISA assays for lg subclasses and anti-DNA antibodies will be used. The cytokine secretion pattern of the inducing and suppressing cells will be compared to help used the different functions of anti-CD1 T cells. The possible role of CD1 molecules as an understand the different function of anti-CD1 T cells. The possible role of CD1 molecules as an autoantigen in heredity mouse models of lipus (NZB/NZW) will be explored also by attempting to block spontaneous autoantibody secretion in vitro and in vivo with anti-CD1 antibodies.