Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
UCLA AIDS Institute, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Cells. 2023 Jan 12;12(2):296. doi: 10.3390/cells12020296.
Humoral immune response is important in fighting pathogens by the production of specific antibodies by B cells. In germinal centers, T follicular helper (TFH) cells provide important help to B-cell antibody production but also contribute to HIV persistence. T follicular regulatory (TFR) cells, which inhibit the function of TFH cells, express similar surface markers. Since FOXP3 is the only marker that distinguishes TFR from TFH cells it is unknown whether the increase in TFH cells observed in HIV infection and HIV persistence may be partly due to an increase in TFR cells. Using multicolor flow cytometry to detect TFH and TFR cells in cryopreserved peripheral blood mononuclear cells from HIV-infected and non-infected participants in the UCLA Multicenter AIDS Cohort Study (MACS), we identified CD3CXCR5CD4CD8BCL6 peripheral blood TFH (pTFH) cells and CD3CXCR5CD4CD8FOXP3 peripheral blood TFR (pTFR) cells. Unlike TFR cells in germinal centers, pTFR cells do not express B cell lymphoma 6 (BCL6), a TFH cell master transcriptional regulator. Our major findings are that the frequency of pTFH cells, but not pTFR cells was higher in HIV-infected participants of the MACS and that pTFH cells expressed less CCR5 in HIV-infected MACS participants. Constitutive expression of CCR5 in TFR cells supports their potential to contribute to HIV persistence.
体液免疫反应通过 B 细胞产生特异性抗体在对抗病原体方面很重要。在生发中心，滤泡辅助性 T 细胞（TFH）为 B 细胞抗体的产生提供了重要帮助，但也促成了 HIV 的持续存在。滤泡调节性 T 细胞（TFR）可抑制 TFH 细胞的功能，它们表达相似的表面标志物。由于 FOXP3 是唯一能将 TFR 细胞与 TFH 细胞区分开来的标志物，因此尚不清楚在 HIV 感染和 HIV 持续存在期间观察到的 TFH 细胞增加是否部分归因于 TFR 细胞的增加。我们使用多色流式细胞术来检测来自感染 HIV 和未感染 HIV 的 UCLA 多中心 AIDS 队列研究（MACS）参与者的冷冻保存外周血单核细胞中的 TFH 和 TFR 细胞，鉴定出 CD3+CXCR5+CD4+CD8+BCL6+外周血 TFH（pTFH）细胞和 CD3+CXCR5+CD4+CD8+FOXP3+外周血 TFR（pTFR）细胞。与生发中心的 TFR 细胞不同，pTFR 细胞不表达 B 细胞淋巴瘤 6（BCL6），这是 TFH 细胞的主要转录调节因子。我们的主要发现是，MACS 中的 HIV 感染者的 pTFH 细胞频率更高，而不是 pTFR 细胞，并且 HIV 感染的 MACS 参与者中的 pTFH 细胞表达的 CCR5 较少。TFR 细胞中 CCR5 的组成型表达支持它们对 HIV 持续存在的潜在贡献。
