Emu Brinda, Sinclair Elizabeth, Hatano Hiroyu, Ferre April, Shacklett Barbara, Martin Jeffrey N, McCune J M, Deeks Steven G
Positive Health Program, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, California, USA.
J Virol. 2008 Jun;82(11):5398-407. doi: 10.1128/JVI.02176-07. Epub 2008 Mar 19.
A rare subset of human immunodeficiency virus (HIV)-infected individuals maintains undetectable HIV RNA levels without therapy ("elite controllers"). To clarify the role of T-cell responses in mediating virus control, we compared HLA class I polymorphisms and HIV-specific T-cell responses among a large cohort of elite controllers (HIV-RNA < 75 copies/ml), "viremic" controllers (low-level viremia without therapy), "noncontrollers" (high-level viremia), and "antiretroviral therapy suppressed" individuals (undetectable HIV-RNA levels on antiretroviral therapy). The proportion of CD4(+) and CD8(+) T cells that produce gamma interferon (IFN-gamma) and interleukin-2 (IL-2) in response to Gag and Pol peptides was highest in the elite and viremic controllers (P < 0.0001). Forty percent of the elite controllers were HLA-B57 compared to twenty-three percent of viremic controllers and nine percent of noncontrollers (P < 0.001). Other HLA class I alleles more common in elite controllers included HLA-B13, HLA-B58, and HLA-B81 (P < 0.05 for each). Within elite and viremic controller groups, those with protective class I alleles had higher frequencies of Gag-specific CD8(+) T cells than those without these alleles (P = 0.01). Noncontrollers, with or without protective alleles, had low-level CD8(+) responses. Thus, certain HLA class I alleles are enriched in HIV controllers and are associated with strong Gag-specific CD8(+)IFN-gamma(+)IL-2(+) T cells. However, the absence of evidence of T cell-mediated control in many controllers suggests the presence of alternative mechanisms for viral control in these individuals. Defining mechanisms for virus control in "non-T-cell controllers" might lead to insights into preventing HIV transmission or preventing virus replication.
一小部分感染人类免疫缺陷病毒（HIV）的个体在未经治疗的情况下可维持检测不到的HIV RNA水平（“精英控制者”）。为了阐明T细胞反应在介导病毒控制中的作用，我们在一大群精英控制者（HIV-RNA<75拷贝/毫升）、“病毒血症控制者”（未经治疗的低水平病毒血症）、“非控制者”（高水平病毒血症）和“抗逆转录病毒治疗抑制”个体（抗逆转录病毒治疗下检测不到HIV-RNA水平）中比较了HLA I类多态性和HIV特异性T细胞反应。精英控制者和病毒血症控制者中，对Gag和Pol肽产生γ干扰素（IFN-γ）和白细胞介素-2（IL-2）的CD4(+)和CD8(+)T细胞比例最高（P<0.0001）。40%的精英控制者为HLA-B57，相比之下，病毒血症控制者为23%，非控制者为9%（P<0.001）。在精英控制者中更常见的其他HLA I类等位基因包括HLA-B13、HLA-B58和HLA-B81（每种P<0.05）。在精英控制者和病毒血症控制者组中，具有保护性I类等位基因的个体中Gag特异性CD8(+)T细胞频率高于没有这些等位基因的个体（P=0.01）。无论有无保护性等位基因，非控制者的CD8(+)反应水平都很低。因此，某些HLA I类等位基因在HIV控制者中富集，并与强大的Gag特异性CD8(+)IFN-γ(+)IL-2(+)T细胞相关。然而，许多控制者中缺乏T细胞介导控制的证据表明这些个体存在病毒控制的替代机制。确定“非T细胞控制者”中病毒控制的机制可能会为预防HIV传播或阻止病毒复制带来启示。
