Valiathan Ranjini, Asthana Deshratn
Department of Pathology, University of Miami-Miller School of Medicine, Miami, FL, USA; Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, Miami, FL, USA.
Department of Pathology, University of Miami-Miller School of Medicine, Miami, FL, USA; Laboratory for Clinical and Biological Studies, University of Miami-Miller School of Medicine, Miami, FL, USA; Department of Psychiatry and Behavioral Science, University of Miami-Miller School of Medicine, Miami, FL, USA.
Immunobiology. 2016 May;221(5):670-8. doi: 10.1016/j.imbio.2016.01.002. Epub 2016 Jan 15.
We analyzed the association of circulating Th-17 cells (cTh-17) with immune activation (IA), immune exhaustion (IE) and regulatory T-cells (T-regs) in 20 human immunodeficiency virus-1 (HIV-1) infected patients with impaired restoration of CD4 T-cell counts despite prolonged suppression of plasma viremia (discordant) and compared it with 20 HIV-1 infected patients showing good immunologic and virologic responses (concordant) following highly active antiretroviral therapy (HAART). Discordant HIV-1 infected patients showed significantly higher frequencies of cTh-17 cells compared to concordant patients and healthy controls after PMA+Ionomicin stimulation. Discordant patients also showed higher CD4 T-cell immune activation (HLA-DR+CD38+) than concordant patients which directly correlated with microbial translocation. Additionally, CD4 T-cells of discordant patients showed higher frequencies of CD4 T-cells expressing multiple immune exhaustion markers (Tim3+PD-1+) which correlated with immune activation indicating that combined analysis of inhibitory molecules along with PD-1 might be a better predictor for immune exhaustion of CD4 T-cells. Increased cTh-17 cell frequency correlated inversely with CD4 T-cell percentages and absolute counts and directly with CD4 T-cell immune activation and T-reg frequencies. Persistent CD4 T-cell immune activation might favor differentiation of activated CD4 T-cells toward cTh-17 phenotype in discordant patients. Discordant patients had significantly lower baseline CD4 T-cell counts and higher viral load at the initiation of HAART and higher immune activation and immune exhaustion after being on HAART for long time indicating that these factors might be associated with an increase in cTh-17 cell frequency, thus, increasing the risk of disease progression despite virologic control.
我们分析了20例人类免疫缺陷病毒1型（HIV-1）感染患者循环Th-17细胞（cTh-17）与免疫激活（IA）、免疫耗竭（IE）及调节性T细胞（T-regs）之间的关联，这些患者尽管血浆病毒血症长期受到抑制，但CD4 T细胞计数恢复受损（不一致组），并将其与20例在高效抗逆转录病毒治疗（HAART）后表现出良好免疫和病毒学反应的HIV-1感染患者（一致组）进行比较。在PMA+离子霉素刺激后，与一致组患者和健康对照相比，不一致组HIV-1感染患者的cTh-17细胞频率显著更高。不一致组患者的CD4 T细胞免疫激活（HLA-DR+CD38+）也高于一致组患者，这与微生物易位直接相关。此外，不一致组患者的CD4 T细胞中表达多种免疫耗竭标志物（Tim3+PD-1+）的CD4 T细胞频率更高，这与免疫激活相关，表明联合分析抑制性分子与PD-1可能是CD4 T细胞免疫耗竭的更好预测指标。cTh-17细胞频率增加与CD4 T细胞百分比和绝对计数呈负相关，与CD4 T细胞免疫激活和T-reg频率呈正相关。持续的CD4 T细胞免疫激活可能有利于不一致组患者中活化的CD4 T细胞向cTh-17表型分化。不一致组患者在HAART开始时基线CD4 T细胞计数显著更低、病毒载量更高，且在接受HAART长时间治疗后免疫激活和免疫耗竭更高，这表明这些因素可能与cTh-17细胞频率增加有关，从而增加了尽管病毒学得到控制但疾病进展的风险。
