Activated dendritic cells and monocytes in HIV immunological nonresponders: HIV-induced interferon-inducible protein-10 correlates with low future CD4+ recovery
Objective: To explore monocyte and dendritic cell immune responses, and their association with future CD4 gain in treated HIV patients with suboptimal CD4 recovery. Design: A cross-sectional study of HIV-infected, virally suppressed individuals on antiretroviral therapy for at least 24 months; 41 immunological nonresponders (INRs) (CD4 cell count <400 cells/μl) and 26 immunological responders (CD4 cell count >600 cells/μl). Ten HIV-infected antiretroviral therapy-naive and 10 HIV-negative healthy persons served as controls. CD4 cell counts were registered after median 2.4 and 4.7 years. Methods: Monocyte, dendritic-cell and T-cell activation and regulatory T cells (Tregs) were analyzed by flow cytometry. In INR and immunological responder subgroups matched on age and nadir CD4 cell count, upregulation of interferon-inducible protein-10 (IP-10) and indoleamine 2,3-dioxygenase in monocytes and dendritic cells and cytokines in cell supernatants were measured in vitro in peripheral blood mononuclear cells stimulated with aldrithiol-2-inactivated HIV-1. Results: The INR group displayed higher spontaneous activation of both monocytes (HLA-DR) and myeloid and plasmacytoid dendritic cells (HLA-DR, CD83 and CD86) compared with immunological responders, and this was associated with increased T-cell activation (CD38HLA-DR), an effector memory T-cell phenotype and activated Tregs. The IP-10 response in monocytes after in-vitro HIV stimulation was negatively associated with prospective CD4 gain. IP-10, indoleamine 2,3-dioxygenase and cytokines levels were comparable between the groups, but inversely correlated with activated Tregs in INRs. Conclusion: HIV-infected individuals with suboptimal immune recovery demonstrated more activated monocytes and in particular dendritic cells, compared with patients with acceptable CD4 gain. A high level of HIV-specific IP-10 expression in monocytes may be predictive of future CD4 recovery.
乐备实(上海优宁维生物科技股份有限公司旗下全资子公司),是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家,自2018年成立以来,乐备实不断寻求突破,公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个,建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。
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