衰老的HIV-1特异性细胞毒性T淋巴细胞中穿孔素和颗粒酶B表达降低。

Decreased perforin and granzyme B expression in senescent HIV-1-specific cytotoxic T lymphocytes.

作者信息

Yang Otto O, Lin Holly, Dagarag Mirabelle, Ng Hwee L, Effros Rita B, Uittenbogaart Christel H

机构信息

Department of Medicine (Division of Infectious Diseases), UCLA Medical Center, Los Angeles, CA 90095-1688, USA.

出版信息

Virology. 2005 Feb 5;332(1):16-9. doi: 10.1016/j.virol.2004.11.028.

DOI:10.1016/j.virol.2004.11.028

PMID:15661136

Abstract

Cytotoxic T lymphocyte (CTL) senescence may be an important mechanism of immune failure in HIV-1 infection. We find that senescence of HIV-1-specific CTL clones causes loss of killing activity, preventable by transduction with telomerase. Furthermore, senescence is associated with reduced expression of the effector molecules granzyme and perforin, suggesting CTL "exhaustion" can result in hypofunction. These results agree with other studies showing that HIV-1-specific CTL exhibit abnormal phenotypes in vivo, and suggest the possibility that chronic turnover is an important mechanism of antiviral failure in HIV-1 infection.

摘要

细胞毒性T淋巴细胞（CTL）衰老可能是HIV-1感染中免疫功能衰竭的一个重要机制。我们发现，HIV-1特异性CTL克隆的衰老会导致杀伤活性丧失，通过端粒酶转导可预防这种情况。此外，衰老与效应分子颗粒酶和穿孔素的表达降低有关，表明CTL“耗竭”可导致功能减退。这些结果与其他研究一致，这些研究表明HIV-1特异性CTL在体内表现出异常表型，并提示慢性更替可能是HIV-1感染中抗病毒失败的一个重要机制。