Swaminathan Sharada, Scorza Tatiana, Yero Alexis, Farnos Omar, Burke Schinkel Stephanie C, Angel Jonathan B, Jenabian Mohammad-Ali
Department of Biological Sciences and CERMO-FC Research Centre, Université du Québec à Montréal (UQAM), Montreal, QC, Canada.
Division of Infectious Diseases, Ottawa Hospital-General Campus, Ottawa, ON, Canada.
Front Microbiol. 2023 Jul 20;14:1217801. doi: 10.3389/fmicb.2023.1217801. eCollection 2023.
The differentiation and function of immunosuppressive regulatory T cells (Tregs) is dictated by the master transcription factor FoxP3. During HIV infection, there is an increase in Treg frequencies in the peripheral blood and lymphoid tissues. This accentuates immune dysfunction and disease progression. Expression of FoxP3 by thymic Tregs (tTregs) is partially controlled by TGF-β. This cytokine also contributes to Treg development in the peripheral blood and lymphoid tissues. Although TGF-β mediates lymphoid tissue fibrosis and peripheral Treg differentiation in HIV-infected individuals, its role in the induction and maintenance of Tregs within the thymus during HIV infection remains unclear.
Thymocytes were isolated from fresh human thymic tissues obtained from pediatric patients undergoing cardiac surgery. Infection by both R5- and X4-tropic HIV-1 strains and TGF-β treatment of human thymocytes was performed in an co-culture model with OP9-DL1 cells expressing Notch ligand delta-like 1 without T cell receptor (TCR) activation.
Despite high expression of CCR5 and CXCR4 by tTregs, FoxP3 + CD3CD8- thymocytes were much less prone to infection with R5- and X4-tropic HIV strains compared to FoxP3-CD3CD8- thymocytes. As expected, CD3CD4+ thymocytes, when treated with TGF-β1, upregulated CD127 and this treatment resulted in increased FoxP3 expression and Treg differentiation, but did not affect the rate of HIV infection. FoxP3 expression and Treg frequencies remained unchanged following HIV infection alone or in combination with TGF-β1.
FoxP3 expression and tTreg differentiation is not affected by HIV infection alone or the combination of HIV infection and TGF-β treatment.
免疫抑制性调节性T细胞（Tregs）的分化和功能由主转录因子FoxP3决定。在HIV感染期间，外周血和淋巴组织中Tregs的频率增加。这加剧了免疫功能障碍和疾病进展。胸腺Tregs（tTregs）中FoxP3的表达部分受转化生长因子-β（TGF-β）控制。这种细胞因子也有助于外周血和淋巴组织中Tregs的发育。尽管TGF-β介导HIV感染个体的淋巴组织纤维化和外周Treg分化，但其在HIV感染期间胸腺内Tregs的诱导和维持中的作用仍不清楚。
从接受心脏手术的儿科患者的新鲜人胸腺组织中分离胸腺细胞。在与表达Notch配体delta样1且无T细胞受体（TCR）激活的OP9-DL1细胞的共培养模型中，用人胸腺细胞进行R5和X4嗜性HIV-1毒株感染以及TGF-β处理。
尽管tTregs高表达CCR5和CXCR4，但与FoxP3-CD3CD8-胸腺细胞相比，FoxP3 + CD3CD8-胸腺细胞感染R5和X4嗜性HIV毒株的可能性要小得多。正如预期的那样，CD3CD4 +胸腺细胞在用TGF-β1处理后，上调了CD127，这种处理导致FoxP3表达增加和Treg分化，但不影响HIV感染率。单独HIV感染或与TGF-β1联合感染后，FoxP3表达和Treg频率保持不变。
单独HIV感染或HIV感染与TGF-β处理的联合均不影响FoxP3表达和tTreg分化。
