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Activated dendritic cells and monocytes in HIV immunological nonresponders: HIV-induced interferon-inducible protein-10 correlates with low future CD4+ recovery.


ABSTRACT:

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/?l) and 26 immunological responders (CD4 cell count >600 cells/?l). 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.

SUBMITTER: Stiksrud B 

PROVIDER: S-EPMC6511429 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Activated dendritic cells and monocytes in HIV immunological nonresponders: HIV-induced interferon-inducible protein-10 correlates with low future CD4+ recovery.

Stiksrud Birgitte B   Aass Hans C D HCD   Lorvik Kristina B KB   Ueland Thor T   Trøseid Marius M   Dyrhol-Riise Anne M AM  

AIDS (London, England) 20190601 7


<h4>Objective</h4>To explore monocyte and dendritic cell immune responses, and their association with future CD4 gain in treated HIV patients with suboptimal CD4 recovery.<h4>Design</h4>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-ne  ...[more]

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