Navis Marjon, Schellens Ingrid M M, van Swieten Peter, Borghans José A M, Miedema Frank, Kootstra Neeltje A, van Baarle Debbie, Schuitemaker Hanneke
Sanquin Research, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam at the Academic Medical Center, Amsterdam, The Netherlands.
J Infect Dis. 2008 Mar 15;197(6):871-9. doi: 10.1086/528695.
The human leukocyte antigen (HLA) B57 allele and the closely related HLA-B5801 allele are overrepresented among human immunodeficiency virus type 1 (HIV-1)-infected individuals with a long-term nonprogressive clinical course of disease (known as "long-term nonprogressors" [LTNPs]). These alleles are, however, also present among individuals with normal disease progression (known as "progressors"). In a comparison of HLA-B57/5801-expressing progressors and LTNPs, we observed a similar prevalence of escape mutations in 4 Nef epitopes and a similar reactivity of CD8+ T cells against 3 of 4 of these epitopes and their autologous escape variants. However, LTNPs tended to have frequent and preserved CD8+ T cell interferon-gamma responses against the wild-type HW9 Nef epitope, whereas progressors did not maintain a specific CD8+ T cell response. This finding is in line with the findings of a more exhausted phenotype of CD8+ T cells in progressors, as is demonstrated by their enhanced level of expression of inhibitory receptor "programmed death 1" (PD-1). The results of the present study suggest that preservation of HW9-specific T cell responses is associated with a more benign clinical course of infection.
人类白细胞抗原（HLA）B57等位基因以及与之密切相关的HLA - B5801等位基因，在1型人类免疫缺陷病毒（HIV - 1）感染且具有长期疾病非进展临床病程的个体（即“长期无进展者”[LTNP]）中过度表达。然而，在疾病正常进展的个体（即“进展者”）中也存在这些等位基因。在对表达HLA - B57/5801的进展者和长期无进展者的比较中，我们观察到在4个Nef表位中逃逸突变的发生率相似，并且CD8 + T细胞对其中4个表位中的3个及其自体逃逸变体的反应性相似。然而，长期无进展者倾向于对野生型HW9 Nef表位有频繁且持续的CD8 + T细胞干扰素 - γ反应，而进展者则未维持特异性CD8 + T细胞反应。这一发现与进展者中CD8 + T细胞具有更耗竭表型的发现一致，这一点通过其抑制性受体“程序性死亡1”（PD - 1）表达水平的提高得以证明。本研究结果表明，HW9特异性T细胞反应的维持与更良性的感染临床病程相关。
