Publications by authors named "Ann W N Auma"

2 Publications

  • Page 1 of 1

Naïve CD4+ T Cell Lymphopenia and Apoptosis in Chronic Hepatitis C Virus Infection Is Driven by the CD31+ Subset and Is Partially Normalized in Direct-Acting Antiviral Treated Persons.

Front Immunol 2021 12;12:641230. Epub 2021 Apr 12.

Department of Pathology, Case Western Reserve University, Cleveland, OH, United States.

Background: The mechanisms underlying naïve CD4+ lymphopenia during chronic Hepatitis C Virus (HCV) infection are unclear. Whether direct-acting antiviral (DAA) therapy restores peripheral naïve CD4+ T cell numbers and function is unknown.

Methods: We enumerated frequencies and counts of peripheral naïve CD4+, CD4+CD31+ and CD4+CD31- T cells by flow cytometry in a cross sectional analysis comparing chronic HCV infected (n=34), DAA-treated(n=29), and age-range matched controls (n=25), as well as in a longitudinal cohort of HCV DAA treated persons (n=16). The cross-sectional cohort was stratified by cirrhosis state. Cell apoptosis/survival (AnnexinV+7AAD+/BCL-2 labeling) and cell cycle entry (Ki67 expression) of CD31+ and CD31- naïve CD4+ T cells was analyzed directly and following 3 and 5 days of culture with media, interleukin (IL) -7 or CD3/CD28 activator.

Results: In the cross-sectional cohort, naïve CD4+ proportions were lower in chronic HCV infected persons compared to controls and DAA-treated persons, an effect in part attributed to cirrhosis. Age was associated with naïve cell counts and proportions in HCV infected and treated persons as well. Naïve CD4+ cell proportions negatively correlated with plasma levels of soluble CD14 following therapy in DAA-treated persons. Naïve CD4+ cells from HCV infected persons exhibited greater direct apoptosis and cell-cycling compared to cells from DAA-treated persons and controls, and this was localized to the CD4+CD31+ subset. On the other hand, no remarkable differences in expression of BCL-2 or IL-7 Receptor (CD127) at baseline or following media or IL7 containing culture were observed. In the longitudinal cohort, naïve CD4+CD31+/CD31- ratio tended to increase 24 weeks after DAA therapy initiation.

Conclusions: Activation and apoptosis of peripheral naïve CD4+CD31+ T cells appear to contribute to naïve CD4+ lymphopenia in chronic HCV infection, and this defect is partially reversible with HCV DAA therapy. Age and cirrhosis -associated naïve CD4+ lymphopenia is present both before and after HCV DAA therapy. These findings have implications for restoration of host immune function after DAA therapy.
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http://dx.doi.org/10.3389/fimmu.2021.641230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075159PMC
April 2021

T-cell Activation Is Correlated With Monocyte Activation in HCV/HIV Coinfection and Declines During HCV Direct-Acting Antiviral Therapy.

Open Forum Infect Dis 2021 Apr 18;8(4):ofab079. Epub 2021 Feb 18.

Department of Pathology, VA Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.

Background: Immune activation markers associate with morbidity and mortality in HIV and hepatitis C virus (HCV) infection. We investigated how T-cell and monocyte activation are related over the course of HCV direct-acting antiviral (DAA) therapy during HCV/HIV coinfection.

Methods: Peripheral blood mononuclear cells from AIDS Clinical Trials Group (ACTG) A5329 participants and a single-site separate cohort treated with DAAs were analyzed for central memory (CM)/effector memory (EM) T-cell subsets, monocyte subsets, and cell activation (CD38 and HLA-DR expression) before, during, and after therapy.

Results: Before therapy, classical and inflammatory monocyte subset HLA-DR expression positively correlated with absolute counts and frequencies of CD38HLA-DR-expressing CD4 and CD8 T cells and corresponding CM and EM subsets. After therapy initiation, CD38HLA-DR co-expression on CD4 and CD8 memory T cells decreased by 12 weeks and 36 weeks, and plasma sCD14 positively correlated with CD38HLA-DR CD4 and CD4CM T-cell frequencies. Monocyte subset activation remained similar over time.

Conclusions: During HCV/HIV coinfection, memory T-cell activation is associated with monocyte subset activation, consistent with related underlying mechanisms. Following therapy initiation, memory T-cell, but not monocyte, activation decreased. Residual CD4 T-cell activation after therapy completion is associated with sCD14, potentially linking the remaining CD4 T-cell activation to residual factors driving activation in antiretroviral therapy-controlled HIV.
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http://dx.doi.org/10.1093/ofid/ofab079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043262PMC
April 2021