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.
Zhang
Yanzheng
Y
Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Stastny
Peter
P
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007111:Immunity, Cellular; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins