Kriegeskorte Anja K, Gebhardt Friedemann E, Porcellini Simona, Schiemann Matthias, Stemberger Christian, Franz Tobias J, Huster Katharina M, Carayannopoulos Leon N, Yokoyama Wayne M, Colonna Marco, Siccardi Antonio G, Bauer Stefan, Busch Dirk H
Institute for Medical Microbiology, Immunology, and Hygiene, Technical University Munich, 81675 Munich, Germany.
Proc Natl Acad Sci U S A. 2005 Aug 16;102(33):11805-10. doi: 10.1073/pnas.0502026102. Epub 2005 Aug 9.
The activating receptor NKG2D recognizes a wide range of different ligands, some of which are primarily expressed in "stressed" tissues or on tumor cells. Until now, similar stimulatory effects on natural killer and CD8+ T cells have been described for all NKG2D ligands, and the NKG2D receptor/ligand system has therefore been interpreted as a sensor system involved in tumor immune surveillance and activation of immune responses. We show here that the NKG2D ligands H60 and MIC class 1 chain-related protein A (MICA) can also mediate strong suppressive effects on T cell proliferation. Responsiveness to H60- and MICA-mediated suppression requires IL-10 and involves a receptor other than NKG2D. These findings might provide explanations for the observation that strong in vivo NKG2D ligand expression, such as that on tumor cells, sometimes fails to support effective immune responses and links this observation to a distinct subgroup of NKG2D ligands.
激活受体NKG2D可识别多种不同的配体，其中一些主要在“应激”组织或肿瘤细胞上表达。到目前为止，所有NKG2D配体对自然杀伤细胞和CD8 + T细胞都有类似的刺激作用，因此NKG2D受体/配体系统被解释为参与肿瘤免疫监视和免疫反应激活的传感系统。我们在此表明，NKG2D配体H60和MHC I类链相关蛋白A（MICA）也可对T细胞增殖介导强烈的抑制作用。对H60和MICA介导的抑制的反应性需要IL-10，并且涉及NKG2D以外的受体。这些发现可能为以下观察结果提供解释：体内强烈的NKG2D配体表达，如肿瘤细胞上的表达，有时无法支持有效的免疫反应，并将这一观察结果与NKG2D配体的一个独特亚组联系起来。
