Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
Cells. 2022 Jul 27;11(15):2307. doi: 10.3390/cells11152307.
Several studies have identified main changes in T- and B-lymphocyte subsets during chronic HIV infection, but few data exist on how these subsets behave during the initial phase of HIV infection. We enrolled 22 HIV-infected patients during the acute stage of infection before the initiation of antiretroviral therapy (ART). Patients had blood samples drawn previous to ART initiation (T0), and at 2 (T1) and 12 (T2) months after ART initiation. We quantified cellular HIV-DNA content in sorted naïve and effector memory CD4 T cells and identified the main subsets of T- and B-lymphocytes using an 18-parameter flow cytometry panel. We identified correlations between the patients' clinical and immunological data using PCA. Effective HIV treatment reduces integrated HIV DNA in effector memory T cells after 12 months (T2) of ART. The main changes in CD4+ T cells occurred at T2, with a reduction of activated memory, cytolytic and activated/exhausted stem cell memory T (T) cells. Changes were present among CD8+ T cells since T1, with a reduction of several activated subsets, including activated/exhausted T. At T2 a reduction of plasmablasts and exhausted B cells was also observed. A negative correlation was found between the total CD4+ T-cell count and IgM-negative plasmablasts. In patients initiating ART immediately following acute/early HIV infection, the fine analysis of T- and B-cell subsets has allowed us to identify and follow main modifications due to effective treatment, and to identify significant changes in CD4+ and CD8+ T memory stem cells.
已有多项研究确定了慢性 HIV 感染过程中 T 淋巴细胞和 B 淋巴细胞亚群的主要变化,但关于这些亚群在 HIV 感染初始阶段的行为方式,仅有少量数据。我们招募了 22 例急性感染期、尚未开始抗逆转录病毒治疗(ART)的 HIV 感染者。患者在开始 ART 治疗前(T0)、治疗后 2 个月(T1)和 12 个月(T2)采集血样。我们对分选的幼稚和效应记忆 CD4 T 细胞中的细胞内 HIV-DNA 含量进行了定量,并使用 18 个参数的流式细胞术面板鉴定了 T 淋巴细胞和 B 淋巴细胞的主要亚群。我们使用 PCA 对患者的临床和免疫数据进行了相关性分析。有效的 HIV 治疗可减少治疗 12 个月(T2)后效应记忆 T 细胞中的整合 HIV DNA。CD4+ T 细胞的主要变化发生在 T2,激活的记忆、细胞毒性和激活/耗竭的干细胞记忆 T(T)细胞减少。从 T1 开始 CD8+ T 细胞就发生了变化,包括激活/耗竭 T 细胞在内的多个激活亚群减少。T2 时也观察到浆母细胞和耗竭 B 细胞减少。总 CD4+ T 细胞计数与 IgM 阴性浆母细胞呈负相关。在急性/早期 HIV 感染后立即开始 ART 的患者中,对 T 淋巴细胞和 B 淋巴细胞亚群的精细分析使我们能够识别和跟踪因有效治疗而发生的主要变化,并确定 CD4+和 CD8+ T 记忆干细胞的显著变化。