MICA antigens stimulate T cell proliferation and cell-mediated cytotoxicity

In previous experiments we have found that transplant recipients had specific antibodies against MICA. In the present study, we measured T cell proliferation, cytokine production, and cytotoxicity to investigate whether immunization with MICA can produce a specific cellular immune response. BALB/c mice were immunized with recombinant MICA (rMICA). Lymphoid cell suspensions obtained after immunization were used to measure T cell proliferation. We detected a robust proliferative response in MICA-stimulated cultures as determined by [3H]thymidine uptake. Using carboxyfluorescein diacetate succinimidyl ester (CFSE) to measure proliferation, we found that in MICA-stimulated cultures, 21% of the CD3+ T cells were CD4+ and CFSE-low and 3% of the T cells were proliferating CD8+ T cells. Among CFSE-low CD4+ spleen cells, 25% secreted IL-4 and only 2% produced IFN-gamma, suggesting a predominant Th2-type response. Blocking of MHC class I or class II molecules with monoclonal antibodies resulted in prominent inhibition of CD8+ or CD4+ T cell proliferation, respectively. In addition, we found that blocking the NKG2D receptor did not cause inhibition of the T cell response. MICA-stimulated CD8+ T lymphocytes exerted cytotoxicity against a BALB/c monocyte cell line (RAW 267.4) primed with soluble rMICA. Our results suggested that MICA-activated T cells may have a role in a cellular component of transplant rejection.