Coordinated expression of ig-like inhibitory MHC class I receptors and acquisition of cytotoxic function in human CD8+ T cells
Coordinated expression of ig-like inhibitory MHC class I receptors and acquisition of cytotoxic function in human CD8+ T cells
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DOI：
10.4049/jimmunol.173.12.7223
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发表时间：
2004-12-15
影响因子：
4.4
通讯作者：
Vivier, E
中科院分区：
文献类型：
--
作者：
Anfossi, N;Doisne, JM;Vivier, E
MHC-I类特异性抑制性受体由记忆表型CD8(+)T细胞亚群表达。与NK细胞类似，MHC-I类特异性抑制性受体可能在T细胞上起重要的负性调控作用，参与预防自体损伤。我们在这里分析了人类CD8(+)T细胞表达Ig样MHC I类特异性抑制受体：杀伤细胞Ig样受体(KIR)和CD85j。免疫球蛋白样抑制性MHC-I受体的细胞表面表达与CD8(+)T细胞成熟的晚期有关，KIR+和CD85j(+)的增殖能力降低证明了这一点。T细胞与其胞浆内高穿孔素含量有关。这种伴随的调节可能代表了一种安全的机制，通过提高CD8(+)T细胞的激活阈值来控制潜在的有害细胞溶解CD8(+)T细胞。然而，KIR+和CD85j(+)T细胞呈现出不同的特征。KIR(+)CD8(+)T细胞在TCR接触时不能产生干扰素-γ。此外，在CMV或HIV-1感染过程中，病毒特异性T细胞表面几乎检测不到KIR。相比之下，CD85j(+)CD8(+)T细胞在TCR触发时产生干扰素-γ，并代表很大一部分病毒特异性T细胞。因此，Ig样抑制性MHC-I受体的细胞表面表达与T细胞参与细胞溶解分化途径的不同阶段有关，CD85j或KIR的细胞表面表达见证了定性和/或定量不同的T细胞激活事件的历史。
MHC class I-specific inhibitory receptors are expressed by a subset of memory-phenotype CD8(+) T cells. Similar to NK cells, MHC class I-specific inhibitory receptors might subserve on T cells an important negative control that participates to the prevention of autologous damage. We analyzed here human CD8(+) T cells that express the Ig-like MHC class I-specific inhibitory receptors: killer cell Ig-like receptor (KIR) and CD85j. The cell surface expression of Ig-like inhibitory MHC class I receptors was found to correlate with an advanced stage of CD8(+) T cell maturation as evidenced by the reduced proliferative potential of KIR+ and CD85j(+). T cells associated with their high intracytoplasmic perforin content. This concomitant regulation might represent a safety mechanism to control potentially harmful cytolytic CD8(+) T cells, by raising their activation threshold. Yet, KIR+ and CD85j(+) T cells present distinct features. KIR(+)CD8(+) T cells are poor IFN-gamma producers upon TCR engagement. In addition, KIR are barely detectable at the surface of virus-specific T cells during the course of CMV or HIV-1 infection. By contrast, CD85j(+)CD8(+) T cells produce IFN-gamma upon TCR triggering, and represent a large fraction of virus-specific T cells. Thus, the cell surface expression of Ig-like inhibitory MHC class I receptors is associated with T cell engagement into various stages of the cytolytic differentiation pathway, and the cell surface expression of CD85j or KIR witnesses to the history of qualitatively and/or quantitatively distinct T cell activation events.