Shacklett B L, Beadle T J, Pacheco P A, Grendell J H, Haslett P A, King A S, Ogg G S, Basuk P M, Nixon D F
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA. bshackle#adarc.org
Virology. 2000 May 10;270(2):317-27. doi: 10.1006/viro.2000.0299.
Acute HIV-1 infection depletes CD4(+) T cells in gut-associated lymphoid tissue (GALT). The failure of containment of local viral replication, and consequent CD4(+) T cell depletion, might be due to delayed mobilization of effector CD8(+) T cells or absence of functioning HIV-1-specific CD8(+) T cell effectors within GALT. No studies have addressed human intestinal HIV-1-specific CD8(+) T cell functions. We sought to determine whether functional HIV-1-specific CTL were present in GALT and whether the repertoire differed from HIV-1-specific CTL isolated from peripheral blood mononuclear cells. From three HIV-1-infected subjects, we isolated HIV-1-specific CD8(+) T cells expressing the mucosal lymphocyte integrin CD103 from GALT. These antigen-specific effector cells could be expanded in vitro and lysed target cells in an MHC class I-restricted manner. HIV-1-specific CTL could be isolated from both duodenal and rectal GALT sites, indicating that CD8(+) effectors were widespread through GALT tissue. The breadth and antigenic specificities of GALT CTL appeared to differ from those in peripheral blood in some cases. In summary, we found HIV-1-specific CD8(+) effector T cells in GALT, despite HIV-1-induced CD4(+) T cell lymphopenia. This suggests that HIV-1-specific CTL in gut tissue can be maintained with limited CD4(+) T cell help.
急性HIV-1感染会使肠道相关淋巴组织（GALT）中的CD4(+) T细胞减少。局部病毒复制无法得到控制以及随之而来的CD4(+) T细胞耗竭，可能是由于效应性CD8(+) T细胞的动员延迟，或者是GALT中缺乏有功能的HIV-1特异性CD8(+) T细胞效应器。尚无研究探讨人类肠道HIV-1特异性CD8(+) T细胞的功能。我们试图确定GALT中是否存在功能性HIV-1特异性CTL，以及其库与从外周血单核细胞中分离出的HIV-1特异性CTL是否不同。我们从三名HIV-1感染受试者的GALT中分离出表达黏膜淋巴细胞整合素CD103的HIV-1特异性CD8(+) T细胞。这些抗原特异性效应细胞可在体外扩增，并以MHC I类限制性方式裂解靶细胞。HIV-1特异性CTL可从十二指肠和直肠GALT部位分离得到，这表明CD8(+)效应器广泛分布于GALT组织中。在某些情况下，GALT CTL的广度和抗原特异性似乎与外周血中的不同。总之，尽管HIV-1导致了CD4(+) T细胞淋巴细胞减少，我们仍在GALT中发现了HIV-1特异性CD8(+)效应T细胞。这表明肠道组织中的HIV-1特异性CTL在有限的CD4(+) T细胞辅助下仍可维持。
