Activated dendritic cells and monocytes in HIV immunological non-responders; HIV-induced IP-10 correlates with low future CD4 recovery


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Abstract

Objective:To explore monocyte and dendritic cell (DC) 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 (ART) for ≥24 months; 41 immunological non-responders (INR) (CD4 < 400 cells/μL) and 26 immunological responders (IR) (CD4 > 600 cells/μL). Ten HIV-infected ART-naive and ten HIV-negative healthy persons served as controls. CD4 counts were registered after median 2.4 and 4.7 years.Methods:Monocyte-, DC-, and T-cell activation and regulatory T cells (Tregs) were analyzed by flow cytometry. In INR and IR subgroups matched on age and nadir CD4 count, upregulation of IP-10 and indoleamine 2, 3 dioxygenase (IDO) in monocytes and DCs and cytokines in cell supernatants were measured in vitro in PBMC stimulated with aldrithiol-2-inactivated HIV-1.Results:The INR group displayed higher spontaneous activation of both monocytes (HLA-DR) and myeloid and plasmacytoid DCs (HLA-DR, CD83 and CD86) compared with IR, and this was associated with increased T-cell activation (CD38+HLA-DR+), an effector memory T-cell phenotype and activated Tregs (aTregs). The IP-10 response in monocytes after in vitro HIV stimulation was negatively associated with prospective CD4 gain. IP-10, IDO and cytokines levels were comparable between the groups, but inversely correlated with aTregs in INR.Conclusion:HIV-infected individuals with suboptimal immune recovery demonstrated more activated monocytes and in particular DCs, 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.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

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