Sheth P M, Chege D, Shin L Y Y, Huibner S, Yue F-Y, Loutfy M, Halpenny R, Persad D, Kovacs C, Chun T-W, Kandel G, Ostrowski M, Kaul R
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Mucosal Immunol. 2008 Sep;1(5):382-8. doi: 10.1038/mi.2008.23. Epub 2008 Jul 2.
Early and profound CD4+ T-cell depletion in gut-associated lymphoid tissue (GALT) may drive Human Immunodeficiency Virus (HIV) immunopathogenesis, and GALT immune reconstitution on highly active antiretroviral therapy (HAART) may be suboptimal. Blood and sigmoid colon biopsies were collected from HAART-treated individuals with undetectable blood HIV RNA for > or =4 years and from uninfected controls. HIV proviral levels and T-cell phenotype/function were examined in both compartments. CD4+ T-cell reconstitution in the sigmoid, including CD4+ T cells expressing CCR5, exceeded that in blood and did not differ from uninfected controls. Sigmoid HIV proviral load was not correlated with CD4+ reconsitution, but was correlated with the degree of mucosal CD8+ T-cell immune activation. Colonic Gag-specific T-cell responses were common, but were not associated with proviral load or immune activation. In this select study population, long-term HAART was associated with complete CD4+ T-cell reconstitution in sigmoid colon. However, colonic immune activation may drive ongoing HIV replication.
肠道相关淋巴组织（GALT）中早期且严重的CD4 + T细胞耗竭可能会推动人类免疫缺陷病毒（HIV）的免疫发病机制，并且在高效抗逆转录病毒疗法（HAART）下GALT的免疫重建可能并不理想。从接受HAART治疗且血液中HIV RNA检测不到≥4年的个体以及未感染的对照中采集血液和乙状结肠活检样本。在两个部位检测HIV前病毒水平和T细胞表型/功能。乙状结肠中CD4 + T细胞的重建，包括表达CCR5的CD4 + T细胞，超过了血液中的重建水平，且与未感染对照无差异。乙状结肠HIV前病毒载量与CD4 + 重建无关，但与黏膜CD8 + T细胞免疫激活程度相关。结肠Gag特异性T细胞反应常见，但与前病毒载量或免疫激活无关。在这个特定的研究人群中，长期HAART与乙状结肠中CD4 + T细胞的完全重建相关。然而，结肠免疫激活可能会推动HIV的持续复制。
