Ibarrondo F Javier, Anton Peter A, Fuerst Marie, Ng Hwee L, Wong Johnson T, Matud Jose, Elliott Julie, Shih Roger, Hausner Mary Ann, Price Charles, Hultin Lance E, Hultin Patricia M, Jamieson Beth D, Yang Otto O
UCLA AIDS Institute, Department of Medicine, Geffen School of Medicine, UCLA Medical Center, Los Angeles, CA 90095, USA.
J Virol. 2005 Apr;79(7):4289-97. doi: 10.1128/JVI.79.7.4289-4297.2005.
Gut-associated lymphoid tissue is the major reservoir of lymphocytes and human immunodeficiency virus type 1 (HIV-1) replication in vivo, yet little is known about HIV-1-specific CD8+ T-lymphocyte (CTL) responses in this compartment. Here we assessed the breadth and magnitude of HIV-1-specific CTL in the peripheral blood and sigmoid colon mucosa of infected subjects not on antiretroviral therapy by enzyme-linked immunospot analysis with 53 peptide pools spanning all viral proteins. Comparisons of blood and mucosal CTL revealed that the magnitude of pool-specific responses is correlated within each individual (mean r2 = 0.82 +/- 0.04) and across all individuals (r2 = 0.75; P < 0.001). Overall, 85.1% of screened peptide pools yielded concordant negative or positive results between compartments. CTL targeting was also closely related between blood and mucosa, with Nef being the most highly targeted (mean of 2.4 spot-forming cells [SFC[/10(6) CD8+ T lymphocytes/amino acid [SFC/CD8/aa]), followed by Gag (1.5 SFC/CD8/aa). Finally, comparisons of peptide pool responses seen in both blood and mucosa (concordant positives) versus those seen only in one but not the other (discordant positives) showed that most discordant results were likely an artifact of responses being near the limit of detection. Overall, these results indicate that HIV-1-specific CTL responses in the blood mirror those seen in the mucosal compartment in natural chronic infection. For protective or immunotherapeutic vaccination, it will be important to determine whether immunity is elicited in the mucosa, which is a key site of initial infection and subsequent HIV-1 replication in vivo.
肠道相关淋巴组织是体内淋巴细胞和1型人类免疫缺陷病毒（HIV-1）复制的主要场所，但对于该区域内HIV-1特异性CD8 + T淋巴细胞（CTL）反应却知之甚少。在此，我们通过酶联免疫斑点分析，使用涵盖所有病毒蛋白的53个肽池，评估了未接受抗逆转录病毒治疗的感染个体外周血和乙状结肠黏膜中HIV-1特异性CTL的广度和强度。血液和黏膜CTL的比较显示，每个个体内肽池特异性反应的强度具有相关性（平均r2 = 0.82±0.04），且在所有个体中也具有相关性（r2 = 0.75；P <0.001）。总体而言，85.1% 的筛选肽池在不同区域间产生了一致的阴性或阳性结果。血液和黏膜之间的CTL靶向也密切相关，Nef是靶向性最高的（平均2.4个斑点形成细胞[SFC]/10(6) CD8 + T淋巴细胞/氨基酸[SFC/CD8/aa]），其次是Gag（1.5 SFC/CD8/aa）。最后，对在血液和黏膜中均可见的肽池反应（一致阳性）与仅在其中一个而非另一个中可见的反应（不一致阳性）进行比较，结果表明，大多数不一致结果可能是由于反应接近检测限所致。总体而言，这些结果表明，在自然慢性感染中，血液中的HIV-1特异性CTL反应反映了黏膜区域中的反应。对于保护性或免疫治疗性疫苗接种而言，确定在黏膜中是否能引发免疫至关重要，因为黏膜是初始感染和体内后续HIV-1复制的关键部位。
