von Geldern Marion, Simm Barbara, Braun Monika, Weiss Elisabeth H, Schendel Dolores J, Falk Christine S
Institute of Molecular Immunology, GSF National Research Center for Environment and Health, Munich, Germany.
Eur J Immunol. 2006 Sep;36(9):2347-58. doi: 10.1002/eji.200535387.
Recent evidence suggests that the functional status of T cells activated independently from their TCR differs substantially from classical MHC-restricted T cells. Here, we show that TCR-independent, short-term stimulation via the common gamma-chain of the IL-2/IL-15 receptor induces non-MHC-restricted cytotoxicity and sustained cytokine secretion in purified CD4+ or CD8+ T cells. NK-like cytotoxicity is directed against MHC class I-negative targets and can be inhibited by classical and non-classical HLA class I molecules. Known inhibitory receptors, such as CD85j (ILT2) and leukocyte-associated Ig-like receptor-1, are not responsible for this HLA-mediated inhibition. NK-like cytotoxicity can be costimulated by NKG2D (CD314) triggering, but 2B4 (CD244) and DNAM-1 (CD226) are not involved. NK-like T cells display an activated phenotype and secrete various cytokines, including IFN-gamma, TNF-alpha, IL-5, IL-13 and MIP-1beta. Under normal conditions, HLA class I-mediated inhibition may function as a safety mechanism to prevent unbalanced cytokine production and effector killing mechanisms by T cells that were activated independently from their TCR. Non-MHC-restricted activity represents a functional status rather than a property of distinct T cell subpopulations. Thus, cytokine-induced, non-MHC-restricted T cells may be relevant in immune responses against tumors showing aberrant MHC expression through their capacities of cytokine production and direct tumor cell eradication.
最近的证据表明，独立于其TCR激活的T细胞的功能状态与经典的MHC限制性T细胞有很大不同。在这里，我们表明，通过IL-2/IL-15受体的共同γ链进行的非TCR依赖性短期刺激可诱导纯化的CD4+或CD8+ T细胞产生非MHC限制性细胞毒性和持续的细胞因子分泌。NK样细胞毒性针对MHC I类阴性靶标，并且可被经典和非经典HLA I类分子抑制。已知的抑制性受体，如CD85j（ILT2）和白细胞相关免疫球蛋白样受体-1，对此HLA介导的抑制作用无作用。NK样细胞毒性可通过NKG2D（CD314）触发共刺激，但不涉及2B4（CD244）和DNAM-1（CD226）。NK样T细胞表现出活化的表型并分泌多种细胞因子，包括IFN-γ、TNF-α、IL-5、IL-13和MIP-1β。在正常情况下，HLA I类介导的抑制作用可能作为一种安全机制，以防止通过独立于其TCR激活的T细胞产生不平衡的细胞因子和效应杀伤机制。非MHC限制性活性代表一种功能状态，而非不同T细胞亚群的特性。因此，细胞因子诱导的非MHC限制性T细胞可能通过其产生细胞因子和直接根除肿瘤细胞的能力，在针对显示异常MHC表达的肿瘤的免疫反应中发挥作用。
