Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection.
Cytotoxic-T-cell responses, viral load, and disease progression in early human immunodeficiency virus type 1 infection.
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DOI：
10.1056/nejm199710303371803
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发表时间：
1997-10
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影响因子：
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通讯作者：
L. Musey;J. Hughes;T. Schacker;T. Shea;L. Corey;L. Corey;M. McElrath;M. McElrath
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文献类型：
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作者：
L. Musey;J. Hughes;T. Schacker;T. Shea;L. Corey;L. Corey;M. McElrath;M. McElrath
背景在人类免疫缺陷病毒1型（HIV-1）感染的早期，病毒复制下降，这归因于宿主免疫，但这种反应的组成部分，特别是细胞毒性T淋巴细胞控制病毒负荷和影响疾病结局的能力，知之甚少。方法我们前瞻性研究了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比较。结果感染后不久，在23例患者中的17例（74%）中检测到主要由CD 8+细胞介导的活化的HIV特异性细胞毒性T淋巴细胞。在感染的前三个月内，在6名接受测试的患者中有6名（100%）发现记忆细胞毒性T淋巴细胞，在前六个月内，在21名接受测试的患者中有17名（81%）发现记忆细胞毒性T淋巴细胞。记忆性细胞毒性T淋巴细胞的频率随时间变化显著，但总体而言，它们在最初的6至8个月内下降，然后在接下来的12至18个月内稳定下来。Env特异性记忆细胞毒性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的患者的三分之一（每毫升RNA拷贝数中位数，22，000 vs. 62，000; P=0.006）。在早期感染中具有低频率Env特异性记忆细胞毒性T淋巴细胞（或无）的患者具有更快的下降至小于300个CD 4+细胞/立方毫米（P = 0.05）。结论：在HIV-1感染早期，记忆性细胞毒性T淋巴细胞的诱导，特别是那些特异于Env的细胞毒性T淋巴细胞，有助于控制病毒复制，并与CD 4+细胞计数下降较慢有关。宿主细胞溶解效应反应似乎可以延缓HIV-1疾病的进展。
BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.