Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection.
Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection.
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DOI：
10.1084/jem.20100090
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发表时间：
2010-12-20
期刊：
影响因子：
--
通讯作者：
Koup RA
中科院分区：
文献类型：
--
作者：
Geldmacher C;Ngwenyama N;Schuetz A;Petrovas C;Reither K;Heeregrave EJ;Casazza JP;Ambrozak DR;Louder M;Ampofo W;Pollakis G;Hill B;Sanga E;Saathoff E;Maboko L;Roederer M;Paxton WA;Hoelscher M;Koup RA
HIV-1优先感染M.结核病特异性CD 4 + T细胞由于其IL-2的产生增加而增加。HIV-1感染导致CD 4 T细胞的进行性丧失。在这项研究中，我们解决了不同的病原体特异性CD 4 T细胞是如何受到艾滋病毒感染和所涉及的细胞参数的影响。我们发现CD 4 T细胞对两种常见的机会致病菌巨细胞病毒（CMV）和结核分枝杆菌（MTB）的消耗率存在显著差异。CMV特异性CD 4 T细胞在HIV感染后持续存在，而MTB特异性CD 4 T细胞迅速耗尽。CMV特异性CD 4 T细胞表达成熟表型，产生非常少的IL-2，但产生大量MIP-1β。相比之下，MTB特异性CD 4 T细胞较不成熟，并且大多数产生IL-2但不产生MIP-1β。在体外实验中，金黄色葡萄球菌肠毒素B刺激的IL-2分泌细胞比MIP-1β分泌细胞更易感染HIV。此外，IL-2的产生与CD 25的表达相关，中和IL-2可以完全消除体外的HIV感染。HIV DNA在产生IL-2的细胞中含量最高，而在活动性结核病HIV感染受试者的产生MIP-1β的MTB特异性CD 4 T细胞中含量最低。这些数据支持这样的假设，即功能差异影响病原体特异性CD 4 T细胞对体内HIV感染和耗竭的易感性，提供了解释HIV感染后MTB特异性CD 4 T细胞快速丧失的潜在机制。
HIV-1 preferentially infects M. tuberculosis-specific CD4+ T cells due to their increased production of IL-2. HIV-1 infection results in the progressive loss of CD4 T cells. In this study, we address how different pathogen-specific CD4 T cells are affected by HIV infection and the cellular parameters involved. We found striking differences in the depletion rates between CD4 T cells to two common opportunistic pathogens, cytomegalovirus (CMV) and Mycobacterium tuberculosis (MTB). CMV-specific CD4 T cells persisted after HIV infection, whereas MTB-specific CD4 T cells were depleted rapidly. CMV-specific CD4 T cells expressed a mature phenotype and produced very little IL-2, but large amounts of MIP-1β. In contrast, MTB-specific CD4 T cells were less mature, and most produced IL-2 but not MIP-1β. Staphylococcal enterotoxin B–stimulated IL-2–producing cells were more susceptible to HIV infection in vitro than MIP-1β–producing cells. Moreover, IL-2 production was associated with expression of CD25, and neutralization of IL-2 completely abrogated productive HIV infection in vitro. HIV DNA was found to be most abundant in IL-2–producing cells, and least abundant in MIP-1β–producing MTB-specific CD4 T cells from HIV-infected subjects with active tuberculosis. These data support the hypothesis that differences in function affect the susceptibility of pathogen-specific CD4 T cells to HIV infection and depletion in vivo, providing a potential mechanism to explain the rapid loss of MTB-specific CD4 T cells after HIV infection.
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COCCHI, F;DEVICO, AL;LUSSO, P
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