Negi Neema, Mojumdar Kamalika, Singh Ravinder, Sharma Ashutosh, Das Bimal Kumar, Sreenivas Vishnubhatla, Vajpayee Madhu
1 Department of Microbiology, All India Institute of Medical Sciences , New Delhi, India .
2 Meakins Christie Laboratories , Montreal, Canada .
Viral Immunol. 2018 Sep;31(7):513-524. doi: 10.1089/vim.2018.0012. Epub 2018 Aug 29.
The exact cause of altered dynamics in T cells compartment during HIV infection remains elusive to date. In this longitudinal study, the proliferation frequency of different T cell subsets was investigated in untreated HIV-1-infected Indian individuals stratified as rapid (R), viremic slow (VS), slow (S) progressors, and healthy controls. Ten healthy and 20 treatment-naive HIV-1-infected individuals were enrolled. Expression of Ki67 nuclear antigen was examined on HIV-specific T cell subsets in peripheral blood lymphocytes. Upon stimulation with HIV-1 Gag-C peptide pools, effector memory (EM) CD4 T cells (R vs. S, EM CD4, p < 0.05) of R progressors proliferated significantly compared with those of S progressors at baseline. However, central memory (CM) CD8 T cell subsets proliferated significantly in VS and S progressors compared with those in R progressors, wherein highest proliferation frequency of EM CD8 T cells was observed. At follow-up visit, the proliferation frequency of naive CD8 T cells was significantly higher in R progressors than S progressors (R vs. S naive CD8, p < 0.05). The findings suggest altered dynamics of different CD4+ and CD8+ T cell subsets in R, VS, and S progressors. The increase in CM T cell proliferation in VS and S progressors could be attributed to slower progression of the HIV infection. Hence, treatment strategies must be focused on restoring the homeostatic balance to restore T cell functionality.
迄今为止,HIV感染期间T细胞区室动力学改变的确切原因仍不清楚。在这项纵向研究中,对未接受治疗的HIV-1感染的印度个体进行了分层,分为快速进展者(R)、病毒血症缓慢进展者(VS)、缓慢进展者(S)和健康对照,研究了不同T细胞亚群的增殖频率。招募了10名健康个体和20名未接受过治疗的HIV-1感染个体。检测外周血淋巴细胞中HIV特异性T细胞亚群上Ki67核抗原的表达。在用HIV-1 Gag-C肽池刺激后,R进展者的效应记忆(EM)CD4 T细胞(R与S,EM CD4,p<0.05)在基线时与S进展者相比增殖显著。然而,与R进展者相比,VS和S进展者的中枢记忆(CM)CD8 T细胞亚群增殖显著,其中观察到EM CD8 T细胞的增殖频率最高。在随访时,R进展者中初始CD8 T细胞的增殖频率显著高于S进展者(R与S初始CD8,p<0.05)。这些发现表明R、VS和S进展者中不同CD4+和CD8+T细胞亚群的动力学发生了改变。VS和S进展者中CM T细胞增殖的增加可能归因于HIV感染进展较慢。因此,治疗策略必须集中于恢复稳态平衡以恢复T细胞功能。