Surface phenotype and functionality of WNV specific T cells differ with age and disease severity.
Surface phenotype and functionality of WNV specific T cells differ with age and disease severity.
复制标题
DOI：
10.1371/journal.pone.0015343
复制
发表时间：
2010-12-13
期刊：
影响因子：
3.7
通讯作者：
Rinaldo CR
中科院分区：
文献类型：
--
作者：
Piazza P;McMurtrey CP;Lelic A;Cook RL;Hess R;Yablonsky E;Borowski L;Loeb MB;Bramson JL;Hildebrand WH;Rinaldo CR
西尼罗河病毒（WNV）感染可导致严重的神经侵袭性疾病，特别是在老年人中。由于啮齿动物模型表明T细胞在限制西尼罗河病毒感染方面发挥重要作用，并且在人类中观察到对西尼罗河病毒的强烈T细胞反应，我们假设抗病毒T细胞免疫不足与神经系统后遗症以及与年龄相关的更严重的结果有关。我们之前报道了6个HLA-A*0201限制性西尼罗河病毒肽表位的发现，自然感染个体的主要T细胞靶点是SVG9 （Env）和SLF9 （NS4b）。在这里，我们评估了40例表现出不同临床症状的西尼罗河病毒血清阳性患者的记忆表型和对这些显性表位的多功能CD8+ T细胞反应。用装载SVG9和SLF9表位的hla - 1多聚体对患者的PBMC进行染色，并用多色流式细胞术进行分析。感染后几个月外周血中发现wnv特异性CD8+ T细胞。老年个体中wnv特异性T细胞的数量与该队列中年轻成员的数量相同，如果不是更多的话。wnv特异性T细胞对CD107a、MIP-1β、TNFα、IL-2或IFNγ主要是单功能的。当CD8+ T细胞反应按疾病严重程度分层时，在病毒神经侵犯患者中检测到终末分化的记忆型（CD45RA+ CD27−CCR7−CD57+） T细胞数量增加。总之，终末分化/细胞溶解型T细胞与神经侵袭有关，而且无论年龄大小，单功能T细胞在感染后持续存在。这些数据首次表明，特定的CD8+ T细胞表型与西尼罗河病毒感染后的疾病结局相关。
West Nile virus (WNV) infection can result in severe neuroinvasive disease, particularly in persons with advanced age. As rodent models demonstrate that T cells play an important role in limiting WNV infection, and strong T cell responses to WNV have been observed in humans, we postulated that inadequate antiviral T cell immunity was involved in neurologic sequelae and the more severe outcomes associated with age. We previously reported the discovery of six HLA-A*0201 restricted WNV peptide epitopes, with the dominant T cell targets in naturally infected individuals being SVG9 (Env) and SLF9 (NS4b). Here, memory phenotype and polyfunctional CD8+ T cell responses to these dominant epitopes were assessed in 40 WNV seropositive patients displaying diverse clinical symptoms. The patients' PBMC were stained with HLA-I multimers loaded with the SVG9 and SLF9 epitopes and analyzed by multicolor flow cytometry. WNV-specific CD8+ T cells were found in peripheral blood several months post infection. The number of WNV-specific T cells in older individuals was the same, if not greater, than in younger members of the cohort. WNV-specific T cells were predominantly monofunctional for CD107a, MIP-1β, TNFα, IL-2, or IFNγ. When CD8+ T cell responses were stratified by disease severity, an increased number of terminally differentiated, memory phenotype (CD45RA+ CD27− CCR7− CD57+) T cells were detected in patients suffering from viral neuroinvasion. In conclusion, T cells of a terminally differentiated/cytolytic profile are associated with neuroinvasion and, regardless of age, monofunctional T cells persist following infection. These data provide the first indication that particular CD8+ T cell phenotypes are associated with disease outcome following WNV infection.
登录
查看更多内容
影响因子：
20.3
作者：
Brenchley, JM;Karandikar, NJ;Koup, RA
通讯作者：
Koup, RA
DOI：
10.1084/jem.20062363
发表时间：
2007-06-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Precopio ML;Betts MR;Parrino J;Price DA;Gostick E;Ambrozak DR;Asher TE;Douek DC;Harari A;Pantaleo G;Bailer R;Graham BS;Roederer M;Koup RA
通讯作者：
Koup RA
DOI：
10.4049/jimmunol.0803903
发表时间：
2009-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Akondy RS;Monson ND;Miller JD;Edupuganti S;Teuwen D;Wu H;Quyyumi F;Garg S;Altman JD;Del Rio C;Keyserling HL;Ploss A;Rice CM;Orenstein WA;Mulligan MJ;Ahmed R
通讯作者：
Ahmed R
影响因子：
6.4
作者：
Murray, Kristy;Walker, Christopher;Fisher-Hoch, Susan
通讯作者：
Fisher-Hoch, Susan
影响因子：
20.3
作者：
Lecuroux, Camille;Girault, Isabelle;Venet, Alain
通讯作者：
Venet, Alain