Decreased Activated CD4 + T Cell Repertoire Diversity After Antiretroviral Therapy in HIV-1/HCV Coinfection Correlates with CD4 + T Cell Recovery

Nicole E. Skinner; Candelaria Vergara; Ramy El-Diwany; Harry Paul; Alyza Skaist; Sarah J. Wheelan; David L. Thomas; Stuart C. Ray; Ashwin Balagopal; Justin R. Bailey

doi:10.1089/vim.2021.0027

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Decreased Activated CD4 + T Cell Repertoire Diversity After Antiretroviral Therapy in HIV-1/HCV Coinfection Correlates with CD4 + T Cell Recovery

Journal article

Peer reviewed

Decreased Activated CD4 + T Cell Repertoire Diversity After Antiretroviral Therapy in HIV-1/HCV Coinfection Correlates with CD4 + T Cell Recovery

Nicole E. Skinner, Candelaria Vergara, Ramy El-Diwany, Harry Paul, Alyza Skaist, Sarah J. Wheelan, David L. Thomas, Stuart C. Ray, Ashwin Balagopal and Justin R. Bailey

Viral immunology, Vol.34(9), pp.622-631

11/01/2021

DOI: 10.1089/vim.2021.0027

PMCID: PMC8917883

PMID: 34672777

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https://www.ncbi.nlm.nih.gov/pmc/articles/8917883View

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Abstract

Dysfunctional immune activation accumulates during chronic viral infection and contributes to disease pathogenesis. In HIV-1, immune activation is exacerbated by concurrent infection with hepatitis C virus (HCV), accelerating depletion of CD4+ T cells. HIV-1 suppression with antiretroviral therapy (ART) generally reconstitutes CD4+ T cell counts, while also reducing the proportion that is activated. Whether this immune reconstitution also reduces the complexity of the CD4+ T cell population is unknown. We sought to characterize the relationship between activated CD4+ T cell repertoire diversity and immune reconstitution following ART in HIV-1/HCV coinfection. We extracted T cell receptor (TCR) sequences from RNA sequencing data obtained from activated CD4+ T cells of HIV-1/HCV coinfected individuals before and after treatment with ART (clinical trial NCT01285050). There was notable heterogeneity in both the extent of CD4+ T cell reconstitution and in the change in activated CD4+ TCR repertoire diversity following ART. Decreases in activated CD4+ TCR repertoire diversity following ART were predictive of the degree of CD4+ T cell reconstitution. The association of decreased activated CD4+ TCR repertoire diversity and improved CD4+ T cell reconstitution may represent loss of nonspecifically activated TCR clonotypes, and possibly selective expansion of specifically activated CD4+ clones. These results provide insight into the dynamic relationship between activated CD4+ TCR diversity and CD4+ T cell recovery of HIV-1/HCV coinfected individuals after suppression of HIV-1 viremia.

Details

Title: Subtitle: Decreased Activated CD4 + T Cell Repertoire Diversity After Antiretroviral Therapy in HIV-1/HCV Coinfection Correlates with CD4 + T Cell Recovery
Creators: Nicole E. Skinner - Johns Hopkins Medicine
Candelaria Vergara - Johns Hopkins Medicine
Ramy El-Diwany - Johns Hopkins University School of Medicine
Harry Paul - Johns Hopkins Medicine
Alyza Skaist - Johns Hopkins University
Sarah J. Wheelan - Johns Hopkins Medicine
David L. Thomas - Johns Hopkins Medicine
Stuart C. Ray - Johns Hopkins University
Ashwin Balagopal - Johns Hopkins Medicine
Justin R. Bailey - Johns Hopkins University
Resource Type: Journal article
Publication Details: Viral immunology, Vol.34(9), pp.622-631
DOI: 10.1089/vim.2021.0027
PMID: 34672777
PMCID: PMC8917883
NLM abbreviation: Viral Immunol
ISSN: 0882-8245
eISSN: 1557-8976
Number of pages: 10
Language: English
Date published: 11/01/2021
Academic Unit: Surgery
Record Identifier: 9984966747202771

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