Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic
Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic
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DOI：
10.1182/blood-2002-03-0791
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发表时间：
2003-01-01
期刊：
影响因子：
20.3
通讯作者：
Lieberman, J
中科院分区：
文献类型：
--
作者：
Zhang, D;Shankar, P;Lieberman, J
尽管HIV特异性CD8 T细胞的频率很高，但大多数HIV感染者在没有抗病毒药物的情况下无法控制病毒复制。虽然CD8T细胞在控制急性HIV和猴免疫缺陷病毒(SIV)感染方面很重要，但在慢性感染中CD8T细胞的功能受到损害。为了探讨功能缺陷是否是HIV特有的，比较了35例HIV感染者和9例健康献血者HIV、EB病毒(EBV)和巨细胞病毒(CMV)特异性CD8T细胞的表型和功能特性。细胞毒性T淋巴细胞表达细胞溶解分子穿孔素和颗粒酶，被认为是CD45RA(+)和CD27(-)。虽然大多数HIV特异性细胞都有抗原经验并表达颗粒酶A(中位数，85%)，但很少有细胞高水平表达穿孔素(中位数，10%)或CD45RA(中位数，14%)或下调CD27(中位数，12%)。在相同的捐赠者或健康捐赠者中，HIV特异性细胞的穿孔素表达与EBV或CMV特异性细胞的表达没有显著差异。EBV和CMV特异性细胞，如HIV特异性细胞，在直接体外测试时通常不具有细胞毒性。其他表型标志物的HIV特异性T细胞的表达与健康献血者中EBV和CMV特异性CD8 T细胞的表达相似。然而，在HIV感染的捐献者中，CMV特异性细胞(在较小程度上，EBV特异性细胞)更有可能是CD27(-)、CD45RA(+)和GzmA(+)。这些结果表明，一旦感染变成慢性感染，通过T细胞介导的裂解来根除感染的机会可能会被破坏。慢性感染期间受损的抗病毒细胞毒性不是HIV所特有的，而可能是对慢性抗原暴露的免疫反应。(C)2003年，由美国血液病学会提供。
Despite the frequency of HIV-specific CD8 T cells, most HIV-infected patients do not control viral replication without antiviral drugs. Although CD8 T cells are important in containing acute HIV and simian immunodeficiency virus (SIV) infection, CD8 T-cell functions are compromised in chronic infection. To investigate whether functional deficits are specific to HIV, the phenotypic and functional properties of HIV, Epstein-Barr virus (EBV), and cytomegalovirus (CMV)-specific CD8 T cells, labeled with HILA A2.1 or B8 tetramers, were compared in 35 HIV-infected and 9 healthy donors. Cytotoxic T lymphocytes express the cytolytic molecules perforin and granzymes, and are thought to be CD45RA(+)CD27(-). Although most HIV-specific cells are antigen experienced and express granzyme A (median, 85%), few express high levels of perforin (median, 10%) or CD45RA (median, 14%) or have down-modulated CD27 (median, 12%). Perforin expression by HIV-specific cells is not significantly different from that of EBV- or CMV-specific cells in the same donors or in healthy donors. EBV- and CMV-specific cells, like HIV-specific cells, are often not cytotoxic when tested directly ex vivo. HIV-specific T-cell expression of other phenotypic markers is similar to that of EBV- and CMV-specific CD8 T cells in healthy donors. However, CMV-specific cells (and, to a lesser extent, EBV-specific cells) in HIV-infected donors are more likely to be CD27(-), CD45RA(+), and GzmA(+). These results suggest that the chance to eradicate an infection by T-cell-mediated lysis may be undermined once an infection becomes chronic. Impaired antiviral cytotoxicity during chronic infection is not specific to HIV but likely represents the immune response to chronic antigenic exposure. (C) 2003 by The American Society of Hematology.