CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection

CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection
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DOI:
10.1182/blood.v98.1.156
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发表时间:
2001-07-01
期刊:
影响因子:
20.3
通讯作者:
Lieberman, J
Lieberman, J
中科院分区:
医学1区
文献类型:
--
作者:
Chen, G;Shankar, P;Lieberman, J

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根据CD 45 RA、CD 62 L和CCR 7的表达,CD 8 T细胞被分为幼稚细胞、效应细胞或记忆细胞。细胞表面CD 62 L和CCR 7受体的顺序接合是通过高内皮微静脉有效运输到淋巴组织所必需的。初始CD 8 T细胞是CCR 7(+)CD 62 L(+)CD 45 RA(+),而长期记忆细胞是CCR 7(+)CD 62 L(+)CD 45 RA(-)。效应细胞毒性T细胞被认为是CCR 7(-)CD 45 RA(+)。比较了健康献血员和HIV阳性献血员的CD 8亚群分布和溶细胞蛋白表达。在HIV感染的受试者中,CCR 7(-)CD 8 T细胞以幼稚和长期记忆细胞为代价扩增。在健康供体和HIV感染供体中,CCR 7(+)CD 8 T细胞对穿孔素均呈阴性。在所有子集中,穿孔素和颗粒酶A不协调表达,穿孔素表达受到更严格的调控。用主要组织相容性复合物肽四聚体染色研究了巨细胞病毒、EB病毒和HIV特异性CD 8 T细胞的特性。这些病毒慢性感染的抗原特异性细胞均为CCR 7-,主要为CD 62 L(-)。在2例HIV血清阳性供体中,与血液共同存在的淋巴结中的EBV四聚体阳性细胞减少了3至4倍。因此,抗原特异性CD 8 T细胞优先从淋巴样部位排除,即使感染主要在淋巴样组织中。这可以保护淋巴组织免受免疫病理学变化的影响,但会损害对靶向淋巴细胞的病毒(如HIV和EBV)的免疫防御。HIV特异性CD 8 T细胞不表达CD 45 RA,而EBV-和CMV-特异性CD 8 T细胞在CD 45 RA(+)表达方面是异质的。缺乏CD 45 RA表达可能表明HIV特异性CD 8 T细胞向细胞毒性T细胞的不完全分化。(C)2001年,美国血液病学会。
CD8 T cells are classified as naive, effector, or memory cells on the basis of CD45RA, CD62L, and CCR7 expression. Sequential engagement of cell-surface CD62L and CCR7 receptors is required for efficient trafficking to lymphoid tissue by means of high endothelial venules, Naive CD8 T cells are CCR7(+)CD62L(+) CD45RA(+), whereas long-term memory cells are CCR7(+)CD62L(+)CD45RA(-). Effector cytotoxic T cells are thought to be CCR7(-)CD45RA(+). The distribution of CD8 subsets and cytolytic protein expression in healthy donors and donors seropositive for human immunodeficiency virus (HIV) were compared. In HIV-infected subjects, CCR7(-) CD8 T cells expanded at the expense of naive and long-term memory cells. In both healthy donors and HIV-infected donors, CCR7(+) CD8 T cells were uniformly negative for perforin. In all subsets, perforin and granzyme A were not coordinately expressed, with perforirr expression being more tightly regulated. The properties of CD8 T cells specific for cytomegalovirus, Epstein-Barr virus (EBV), and HIV were studied by staining with major histocompatibility complex peptide tetramers, Antigen-specific cells for chronic infections with these viruses were uniformly CCR7- and predominantly CD62L(-). In 2 HIV-seropositive donors, 3-to 4-fold fewer EBV-tetramer-positive cells were present in lymph nodes com-pared with blood. Antigen-specific CD8 T cells are therefore preferentially excluded from lymphoid sites, even when infection is primarily in lymphoid tissue. This may protect lymphoid tissues from immunopathological changes but compromise immune defense against viruses, such as HIV and EBV, that target lymphocytes. HIV-specific CD8 T cells do not express CD45RA, whereas EBV- and CMV-specific CD8 T cells are heterogeneous in CD45RA(+) expression, Lack of CD45RA expression may indicate incomplete differentiation of HIV-specific CD8 T cells to cytotoxic T cells. (C) 2001 by The American Society of Hematalogy.