Musey L, Hughes J, Schacker T, Shea T, Corey L, McElrath M J
Department of Medicine, School of Medicine, University of Washington, Seattle, USA.
N Engl J Med. 1997 Oct 30;337(18):1267-74. doi: 10.1056/NEJM199710303371803.
Early in human immunodeficiency virus type 1 (HIV-1) infection there is a decline in viral replication that has been attributed to host immunity, but the components of this response, particularly the ability of cytotoxic T lymphocytes to control viral burden and influence the outcome of disease, are poorly understood.
We prospectively studied 33 patients with primary HIV-1 infection for HIV-specific activated cytotoxic T lymphocytes and memory cytotoxic T lymphocytes and compared these lymphocyte responses with changes in viral load and clinical status over the subsequent 18 to 24 months.
Soon after infection, activated HIV-specific cytotoxic T lymphocytes, mediated primarily by CD8+ cells, were detected in 17 of 23 patients (74 percent). Memory cytotoxic T lymphocytes were found in 6 of 6 patients tested (100 percent) during the first three months of infection and in 17 of 21 patients (81 percent) tested during the first six months. The frequencies of memory cytotoxic T lymphocytes varied markedly over time, but overall they declined over the first 6 to 8 months and then stabilized over the next 12 to 18 months. The patients with higher frequencies of Env-specific memory cytotoxic T lymphocytes had a median level of plasma HIV-1 RNA about one third that of the patients with lower frequencies, (median number of RNA copies per milliliter, 22,000 vs. 62,000; P=0.006). Patients with low frequencies of Env-specific memory cytotoxic T lymphocytes (or none) in early infection had a more rapid decline to less than 300 CD4+ cells per cubic millimeter (P = 0.05).
In early HIV-1 infection, the induction of memory cytotoxic T lymphocytes, particularly those specific for Env, helps control viral replication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease.
在人类免疫缺陷病毒1型（HIV-1）感染早期，病毒复制会下降，这被认为归因于宿主免疫，但这种反应的组成部分，尤其是细胞毒性T淋巴细胞控制病毒载量和影响疾病结局的能力，目前了解甚少。
我们前瞻性地研究了33例原发性HIV-1感染患者的HIV特异性活化细胞毒性T淋巴细胞和记忆性细胞毒性T淋巴细胞，并将这些淋巴细胞反应与随后18至24个月内病毒载量和临床状态的变化进行了比较。
感染后不久，在23例患者中的17例（74%）检测到主要由CD8+细胞介导的活化HIV特异性细胞毒性T淋巴细胞。在感染的前三个月，6例接受检测的患者中有6例（100%）发现了记忆性细胞毒性T淋巴细胞，在感染的前六个月，21例接受检测的患者中有17例（81%）发现了记忆性细胞毒性T淋巴细胞。记忆性细胞毒性T淋巴细胞的频率随时间显著变化，但总体而言，它们在最初的6至8个月下降，然后在接下来的12至18个月稳定下来。Env特异性记忆性细胞毒性T淋巴细胞频率较高的患者血浆HIV-1 RNA的中位数水平约为频率较低患者的三分之一（每毫升RNA拷贝数中位数，22,000对62,000；P=0.006）。早期感染时Env特异性记忆性细胞毒性T淋巴细胞频率低（或无）的患者CD4+细胞计数下降至每立方毫米少于300个的速度更快（P=0.05）。
在HIV-1感染早期，记忆性细胞毒性T淋巴细胞的诱导，尤其是针对Env的记忆性细胞毒性T淋巴细胞，有助于控制病毒复制，并与CD4+细胞计数下降较慢有关。宿主溶细胞效应反应似乎会延迟HIV-1疾病的进展。
