Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection
Weak anti-HIV CD8+ T-cell effector activity in HIV primary infection
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DOI：
10.1172/jci7162
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发表时间：
1999-11-01
影响因子：
15.9
通讯作者：
Venet, A
中科院分区：
文献类型：
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作者：
Dalod, M;Dupuis, M;Venet, A
HIV特异性CD8(+) T细胞在HIV原发感染（PI）期间的病毒控制中发挥主要作用，但不能完全阻止病毒复制。我们使用ifn - γ酶联免疫斑点法和细胞内染色来表征24例早期HIV PI患者体内CD8(+) t细胞对多种HIV表位肽的反应。我们观察到71%的受试者有hiv特异性反应。Gag和Nef肽比Env和Pol肽更容易被识别。识别的多肽数量较低（中位数2，范围0-6）。相比之下，在30名无症状的慢性感染患者中观察到更广泛的反应：所有应答者中位数为5个肽被识别（范围1-13）。对于给定肽，两组PBMC中hiv特异性CD8(+) T细胞的频率是相同的数量级。hiv特异性CD8(+)CD28（-）终末分化T细胞在PI中的比例远低于慢性感染阶段。HN PI期间免疫反应的薄弱可能部分解释了无法控制HIV的原因。这些发现对于确定免疫治疗策略和建立有效疫苗接种目标具有潜在的重要性。
HIV-specific CD8(+) T cells play a major role in the control of virus during HIV primary infection (PI) but do not completely prevent viral replication. We used IFN-gamma enzyme-linked immunospot assay and intracellular staining to characterize the ex vivo CD8(+) T-cell responses to a large variety of HIV epitopic peptides in 24 subjects with early HIV PI. We observed HIV-specific responses in 71% of subjects. Gag and Nef peptides were more frequently recognized than Env and Pol peptides. The number of peptides recognized was low (median 2, range 0-6). In contrast, a much broader response was observed in 30 asymptomatic subjects with chronic infection: all were responders with a median of 5 peptides recognized (range 1-13). The frequency of HIV-specific CD8(+) T cells among PBMC for a given peptide was of the same order of magnitude in both groups. The proportion of HIV-specific CD8(+)CD28(-) terminally differentiated T cells was much lower in PI than at the chronic stage of infection. The weakness of the immune response during HN PI could partially account for the failure to control HIV. These findings have potential importance for defining immunotherapeutic strategies and establishing the goals for effective vaccination.