Williams Cortny A, Murray Susan E, Weinberg Andrew D, Parker David C
Department of Molecular Microbiology and Immunology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
J Immunol. 2007 Jun 15;178(12):7694-702. doi: 10.4049/jimmunol.178.12.7694.
Ag-specific CD4 T cells transferred into unirradiated Ag-bearing recipients proliferate, but survival and accumulation of proliferating cells is not extensive and the donor cells do not acquire effector functions. We previously showed that a single costimulatory signal delivered by an agonist Ab to OX40 (CD134) promotes accumulation of proliferating cells and promotes differentiation to effector CD4 T cells capable of secreting IFN-gamma. In this study, we determined whether OX40 costimulation requires supporting costimulatory or differentiation signals to drive acquisition of effector T cell function. We report that OX40 engagement drives effector T cell differentiation in the absence of CD28 and CD40 signals. Two important regulators of Th1 differentiation, IL-12R and T-bet, also are not required for acquisition of effector function in CD4 T cells responsive to OX40 stimulation. Finally, we show that CD25-deficient CD4 T cells produce little IFN-gamma in the presence of OX40 costimulation compared with wild type, suggesting that IL-2R signaling is required for efficient OX40-mediated differentiation to IFN-gamma secretion.
转移至未受照射的携带抗原受体中的抗原特异性CD4 T细胞会增殖，但增殖细胞的存活和积累并不广泛，且供体细胞不会获得效应功能。我们之前表明，激动剂抗体向OX40（CD134）传递的单一共刺激信号可促进增殖细胞的积累，并促进其分化为能够分泌γ干扰素的效应CD4 T细胞。在本研究中，我们确定OX40共刺激是否需要支持性共刺激或分化信号来驱动效应T细胞功能的获得。我们报告称，在没有CD28和CD40信号的情况下，OX40激活可驱动效应T细胞分化。对于响应OX40刺激的CD4 T细胞获得效应功能而言，Th1分化的两个重要调节因子IL-12R和T-bet也并非必需。最后，我们表明，与野生型相比，在存在OX40共刺激的情况下，缺乏CD25的CD4 T细胞产生的γ干扰素很少，这表明IL-2R信号传导是OX40介导的向分泌γ干扰素分化的有效进行所必需的。
