Preservation of T cell proliferation restricted by protective HLA alleles is critical for immune control of HIV-1 infection
Preservation of T cell proliferation restricted by protective HLA alleles is critical for immune control of HIV-1 infection
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DOI：
10.4049/jimmunol.177.10.7406
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发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
McElrath, M. Juliana
中科院分区：
文献类型：
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作者：
Horton, Helen;Frank, Ian;McElrath, M. Juliana
携带HLA-B27和-B57等位基因的HIV-1感染者通常在没有抗逆转录病毒治疗的情况下保持健康数十年。受这些等位基因限制的CD 8（+）T细胞的特性被认为在这些个体中赋予疾病保护是难以捉摸的，但理解并通过疫苗接种潜在地引发是重要的。为了解决这个问题，我们使用多色流式细胞术比较了HIV-1免疫原和自然感染诱导的CD 8（+）T细胞功能。来自所有4名未感染的免疫受试者和21名感染受试者的HIV-1特异性CD 8（+）T细胞分泌IFN-γ和TNF-α。然而，由疫苗接种和初次感染而非慢性感染诱导的CD 8（+）T细胞增殖至其同源表位。值得注意的是，来自非进展者的B27-和B57-限制性CD 8（+）T细胞比那些受其他等位基因限制的细胞表现出更大的扩增。因此，受某些保护性等位基因限制的CD 8（+）T细胞可以抵抗复制缺陷，这允许扩增和抗病毒效应物活性。我们的研究结果表明，无论MHC限制如何，维持CD 8（+）T细胞增殖的能力可能是疫苗接种后感染时疾病保护的重要相关因素。
HIV-1-infected persons with HLA-B27 and -B57 alleles commonly remain healthy for decades without antiretroviral therapy. Properties of CD8(+) T cells restricted by these alleles considered to confer disease protection in these individuals are elusive but important to understand and potentially elicit by vaccination. To address this, we compared CD8(+) T cell function induced by HIV-1 immunogens and natural infection using polychromatic flow cytometry. HIV-1-specific CD8(+) T cells from all four uninfected immunized and 21 infected subjects secreted IFN-gamma and TNF-alpha. However, CD8(+) T cells induced by vaccination and primary infection, but not chronic infection, proliferated to their cognate epitopes. Notably, B27- and B57-restricted CD8(+) T cells from nonprogressors exhibited greater expansion than those restricted by other alleles. Hence, CD8(+) T cells restricted by certain protective alleles can resist replicative defects, which permits expansion and antiviral effector activities. Our findings suggest that the capacity to maintain CD8(+) T cell proliferation, regardless of MHC-restriction, may serve as an important correlate of disease protection in the event of infection following vaccination.