Vingert Benoit C, Le Grand Roger, Venet Alain
Laboratoire Inserm E0109, Faculté de Médecine-Paris Sud, 63, rue Gabriel-Péri, 94276 Kremlin-Bicêtre cedex, France.
Microbes Infect. 2003 Jul;5(9):757-67. doi: 10.1016/s1286-4579(03)00144-8.
Virus-specific CD8(+) T cells play an important role in controlling viral replication during acute primary infection. At this early stage, mucosal tissues represent a major site of viral replication. Therefore, the presence of functional virus-specific CD8(+) effector T cells in the mucosa during primary infection is a key issue in the pathogenesis of infection. In order to evaluate the extent of this response, six rhesus macaques were infected with simian immunodeficiency virus (SIV)mac251 and sacrificed on day 28 following infection. The functional activity of SIV-effector CD8(+) T cells was evaluated by means of a gamma-IFN ELISpot assay with autologous cells expressing SIV env, gag, pol and nef genes as antigen-presenting cells. This evaluation was performed on PBMCs, spleen, peripheral lymph node, gut-associated lymph node and lamina propria lymphocytes isolated from different mucosal sites. In parallel, the cell-associated viral load was quantified in all these tissues. Five macaques had gamma-IFN SIV-specific CD8(+) T cells in PBMCs and/or lymph nodes. However, in these macaques, these CD8(+) T cells were only present in seven mucosal sites out of 24 tested (the lamina propria lymphocytes of the duodenum, jejunum, ileum and colon were evaluated separately for each animal), whereas they were detected in all corresponding gut-associated lymph nodes. In addition, the mean frequency of SIV-specific gamma-IFN-secreting CD8(+) T cells was 117 +/- 228 per 10(6) cells in the lamina propria vs. 958 +/- 1184 in gut associated lymph nodes (P = 0.001). No overall correlation was observed between the CD8(+) T-cell activity and the viral load: among the 17 mucosal sites in which the virus was isolated, no specific activity was detected in 13 sites. In conclusion, these data indicate that the frequencies of SIV-specific gamma-IFN-secreting CD8(+) T cells are low in the mucosa during early primary infection. This may be of importance with regard to the intense viral replication observed in the mucosa at this stage.
病毒特异性CD8(+) T细胞在急性初次感染期间控制病毒复制方面发挥着重要作用。在这个早期阶段，黏膜组织是病毒复制的主要部位。因此，初次感染期间黏膜中功能性病毒特异性CD8(+) 效应T细胞的存在是感染发病机制中的一个关键问题。为了评估这种反应的程度，六只恒河猴感染了猴免疫缺陷病毒（SIV）mac251，并在感染后第28天处死。通过γ-干扰素酶联免疫斑点分析（ELISpot）评估SIV效应性CD8(+) T细胞的功能活性，使用表达SIV env、gag、pol和nef基因的自体细胞作为抗原呈递细胞。对从不同黏膜部位分离的外周血单核细胞（PBMC）、脾脏、外周淋巴结、肠道相关淋巴结和固有层淋巴细胞进行了该评估。同时，对所有这些组织中的细胞相关病毒载量进行了定量。五只猕猴的PBMC和/或淋巴结中有γ-干扰素SIV特异性CD8(+) T细胞。然而，在这些猕猴中，这些CD8(+) T细胞仅在24个测试的黏膜部位中的7个部位存在（每只动物分别评估十二指肠、空肠、回肠和结肠的固有层淋巴细胞），而在所有相应的肠道相关淋巴结中均检测到它们。此外，固有层中分泌SIV特异性γ-干扰素的CD8(+) T细胞的平均频率为每10(6) 个细胞117±228，而在肠道相关淋巴结中为958±1184（P = 0.001）。未观察到CD8(+) T细胞活性与病毒载量之间的总体相关性：在分离出病毒的17个黏膜部位中，13个部位未检测到特异性活性。总之，这些数据表明，在初次感染早期，黏膜中分泌SIV特异性γ-干扰素的CD8(+) T细胞频率较低。这对于在此阶段在黏膜中观察到的强烈病毒复制可能具有重要意义。
