14 February 2019
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To explore monocyte and dendritic cell immune responses, and their association with future CD4 + gain in treated HIV patients with suboptimal CD4 + recovery.
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.
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.
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 (CD38 +HLA-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.