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T CELL RESPONSES TO MICA.
Y. Zhang, MD and P. Stastny, MD. Dallas TX, UT Southwestern Med Cntr, Internal Medicine.
In previous experiments we have shown that humans and mice when exposed to MICA readily produce antibodies against this antigen. In the present study, we investigated whether immunization with MICA can also produce a specific cellular immune response, by measuring T cell proliferation and cytokine production. BALB/c mice were immunized with rMICA or cells expressing MICA by transfection. Lymphoid cell suspensions obtained 14 days after immunization were stained with carboxyfluorescein (CFSE) and cultured with soluble rMICA, KLH or mumps antigen for 6 days. In parallel cultures, H3Tdr was added on the fifth day of culture to measure thymidine uptake. We found that in the MICA-antigen treated cultures populations of CFSE-low CD4+ and CD8+ T lymphocytes emerged, which represented 44% and 8% of the cells in culture. Comparatively, when spleen cells from mice immunized with MICA were cultured with mumps or KLH antigen, practically no CFSE-low cells developed, suggesting that the CFSE-low population emerges due to antigen-specific stimulation. The size of the CFSE-low CD3+ spleen cell population significantly correlated with cell proliferation as measured by H3Tdr uptake. We investigated the production of IFN-r, TNF-α, IL-4 and IL-5 and found that CFSE-low CD4+ spleen cells displayed marked increase in IL-4 and IL-5 production and no difference in IFN-r or TNF-α production between MICA-stimulated and controls. This suggested a predominant Th2-type response. Experiments are underway to determine whether MICA-specific CD4+T cells are activated through their αβTCR, or through NKG2D engagement, whether T cell responses to MICA are restricted to classical MHC molecules and whether the activated proliferating CD8+ T cells can mediate cytotoxicity and therefore possibly have a role in transplant rejection elicited by allogeneic MICA.