Strickland Natalie, Müller Tracey L, Berkowitz Natacha, Goliath Rene, Carrington Mary N, Wilkinson Robert J, Burgers Wendy A, Riou Catherine
Division of Medical Virology, Department of Pathology, Faculty of Health Sciences, University of Cape Town, 7925 Cape Town, South Africa.
Institute of Infectious Disease and Molecular Medicine, University of Cape Town, 7925 Cape Town, South Africa.
J Immunol. 2017 Oct 1;199(7):2440-2450. doi: 10.4049/jimmunol.1700849. Epub 2017 Aug 9.
A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4 T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of -specific CD4 T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using -specific MHC class II tetramers. We examined the phenotype as well as function of ex vivo -specific tetramerCD4 T cells using flow cytometry. The numbers of -specific tetramerCD4 T cells were relatively well maintained in HIV-infected persons with aTB, despite severe immunodeficiency. However, although HIV-uninfected persons with latent TB infection exhibited ex vivo -specific CD4 T cells predominantly of a CXCR3CCR6CCR4 (Th1*) phenotype, aTB or HIV infection was associated with a contraction of this subset. Nevertheless, in individuals with aTB and/or HIV infection, circulating ex vivo -specific CD4 T cells did not display defects in exhaustion or polyfunctionality compared with healthy HIV-uninfected individuals with latent TB infection. Collectively, these data suggest that increased susceptibility to TB disease could be related to a loss of circulating Th1* CD4 T cells rather than major changes in the number or function of circulating CD4 T cells.
开发一种有效的抗结核疫苗面临的一个主要挑战是，针对人类结核病的保护性CD4 T细胞反应的特性仍然难以捉摸。感染1型人类免疫缺陷病毒（HIV）是患结核病的一个主要风险因素，更好地了解HIV引起的特异性CD4 T细胞改变导致宿主抵抗力下降，可能有助于深入了解针对结核病的保护性T细胞免疫。使用特异性MHC II类四聚体对来自结核病流行地区的86名参与者进行了筛查，这些参与者要么感染了HIV，要么未感染HIV，患有潜伏性或活动性结核病（aTB）。我们使用流式细胞术检查了体外特异性四聚体CD4 T细胞的表型和功能。尽管存在严重免疫缺陷，但在患有aTB的HIV感染者中，特异性四聚体CD4 T细胞的数量相对保持良好。然而，尽管未感染HIV的潜伏性结核感染者的体外特异性CD4 T细胞主要表现为CXCR3CCR6CCR4（Th1*）表型，但aTB或HIV感染与该亚群的收缩有关。尽管如此，与未感染HIV的潜伏性结核感染健康个体相比，患有aTB和/或HIV感染的个体中，循环的体外特异性CD4 T细胞在耗竭或多功能性方面没有表现出缺陷。总的来说，这些数据表明，对结核病易感性增加可能与循环Th1* CD4 T细胞的丧失有关，而不是循环CD4 T细胞数量或功能的重大变化。
