Detection of polyfunctional Mycobacterium tuberculosis-specific T cells and association with viral load in HIV-1-infected persons
Detection of polyfunctional Mycobacterium tuberculosis-specific T cells and association with viral load in HIV-1-infected persons
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DOI：
10.1086/529048
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发表时间：
2008-04-01
影响因子：
6.4
通讯作者：
Walker, Bruce D.
中科院分区：
文献类型：
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作者：
Day, Cheryl L.;Mkhwanazi, Nompumelelo;Walker, Bruce D.
背景人类免疫缺陷病毒1型（HIV-1）的流行与结核病（TB）发病率的显著增加相关;然而，对合并感染个体中结核分枝杆菌（MTB）特异性细胞免疫应答的质量知之甚少。在南非德班，共137例HIV-1阳性个体，在干扰素（IFN）-γ酶联免疫斑点（ELISPOT）试验中使用跨越Ag 85 A、培养滤液蛋白10（CFP-10）、早期分泌抗原靶标6（ESAT-6）和TB 10. 4的重叠肽进行筛选。对MTB特异性产生的IFN-γ、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-2进行细胞内细胞因子染色，并对MTB特异性T细胞上的记忆标记物进行离体表型分析。共有41%的受试者对ESAT-6和/或CFP-10有反应，表明存在潜伏性MTB感染。MTB特异性IFN-γ（+）/TNF-α（+）CD 4（+）细胞的比例显著高于IFN-γ（+）/IL-2（+）CD 4（+）细胞的比例（P = .0220），MTB特异性IL-2分泌CD 4细胞的比例与HIV-1载量呈负相关（P = .0098）。MTB特异性CD 8 T细胞主要是IFN-γ（+）/TNF-α（+）/IL-2（-）。MTB特异性CD 4和CD 8 T细胞的离体记忆表型表明效应记忆细胞群体的早期至中期分化表型。在没有活动性疾病的情况下，多功能MTB特异性CD 4和CD 8 T细胞应答维持在HIV-1阳性个体的外周血中，并且这些应答的功能能力受到HIV-1疾病状态的影响。
Background. The human immunodeficiency virus type 1 ( HIV-1) epidemic is associated with a significant increase in the incidence of tuberculosis ( TB); however, little is known about the quality of Mycobacterium tuberculosis ( MTB)-specific cellular immune responses in coinfected individuals.Methods. A total of 137 HIV-1-positive individuals in Durban, South Africa, were screened with the use of overlapping peptides spanning Ag85A, culture filtrate protein 10 ( CFP-10), early secretory antigen target 6 ( ESAT-6), and TB10.4, in an interferon ( IFN)-gamma enzyme-linked immunospot ( ELISPOT) assay. Intracellular cytokine staining for MTB-specific production of IFN-gamma, tumor necrosis factor ( TNF)-alpha, and interleukin ( IL)-2 was performed, as was ex vivo phenotyping of memory markers on MTB-specific T cells.Results. A total of 41% of subjects responded to ESAT-6 and/or CFP-10, indicating the presence of latent MTB infection. The proportion of MTB-specific IFN-gamma(+)/TNF-alpha(+) CD4(+) cells was significantly higher than the proportion of IFN-gamma(+)/IL-2(+) CD4(+) cells ( P = .0220), and the proportion of MTB- specific IL-2-secreting CD4 cells was inversely correlated with the HIV-1 load ( P = .0098). MTB- specific CD8 T cells were predominately IFN-gamma(+)/TNF-alpha(+)/IL-2(-). Ex vivo memory phenotyping of MTB- specific CD4 and CD8 T cells indicated an early to intermediate differentiated phenotype for the population of effector memory cells.Conclusions. Polyfunctional MTB- specific CD4 and CD8 T cell responses are maintained in the peripheral blood of HIV-1-positive individuals, in the absence of active disease, and the functional capacity of these responses is affected by HIV-1 disease status.