Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection
Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection
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DOI：
10.1182/blood-2010-11-317297
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发表时间：
2011-05-05
期刊：
影响因子：
20.3
通讯作者：
Koup, Richard A.
中科院分区：
文献类型：
--
作者：
Yamamoto, Takuya;Price, David A.;Koup, Richard A.
共抑制和共刺激受体的高度复杂网络调节病毒特异性CD 8（+）T细胞应答的结果。在这里，我们报告了HIV特异性、巨细胞病毒特异性和大量CD 8（+）T细胞记忆群体中多种抑制性受体的表达模式。与巨细胞病毒特异性CD 8（+）T细胞相反，大多数HIV特异性CD 8（+）T细胞表现出不成熟的表型，并表达程序性死亡-1，CD 160和2B 4，但不表达淋巴细胞活化基因-3。值得注意的是，在抗逆转录病毒治疗之前，这些负调节因子的同时表达与HIV载量和受损的细胞因子产生强烈相关。抗逆转录病毒治疗对HIV复制的抑制与HIV特异性CD 8（+）T细胞表面抑制分子表达减少有关。此外，在体外操纵程序性死亡-1和2B 4抑制途径增加了HIV特异性CD 8（+）T细胞的增殖能力。因此，多种共抑制受体可以影响HIV特异性CD 8（+）T细胞反应的发展，并通过扩展，代表HIV感染者中新的基于免疫的干预措施的潜在靶点。（血。2011; 117（18）：4805-4815）
A highly complex network of coinhibitory and costimulatory receptors regulates the outcome of virus-specific CD8(+) T-cell responses. Here, we report on the expression patterns of multiple inhibitory receptors on HIV-specific, cytomegalovirusspecific, and bulk CD8(+) T-cell memory populations. In contrast to cytomegalovirus-specific CD8(+) T cells, the majority of HIV-specific CD8(+) T cells exhibited an immature phenotype and expressed Programmed Death-1, CD160 and 2B4 but not lymphocyte activation gene-3. Notably, before antiretroviral therapy, simultaneous expression of these negative regulators correlated strongly with both HIV load and impaired cytokine production. Suppression of HIV replication by antiretroviral therapy was associated with reduced surface expression of inhibitory molecules on HIV-specific CD8(+) T cells. Furthermore, in vitro manipulation of Programmed Death-1 and 2B4 inhibitory pathways increased the proliferative capacity of HIV-specific CD8(+) T cells. Thus, multiple coinhibitory receptors can affect the development of HIV-specific CD8(+) T-cell responses and, by extension, represent potential targets for new immune-based interventions in HIV-infected persons. (Blood. 2011; 117(18): 4805-4815)