Work

Dominant CD4+ T cell receptors remain stable throughout antiretroviral therapy-mediated immune restoration in people with HIV

Year: 2023

Type: article

Study design: Observational Study

Abstract: In people with HIV (PWH), the post-antiretroviral therapy (ART) window is critical for immune restoration and HIV reservoir stabilization. We employ deep immune profiling and T cell receptor (TCR) sequencing and examine proliferation to assess how ART impacts T cell homeostasis. In PWH on long-term ART, lymphocyte frequencies and phenotypes are mostly stable. By contrast, broad phenotypic changes in natural killer (NK) cells, γδ T cells, B cells, and CD4 + and CD8 + T cells are observed in the post-ART window. Whereas CD8 + T cells mostly restore, memory CD4 + T subsets and cytolytic NK cells show incomplete restoration 1.4 years post ART. Surprisingly, the hierarchies and frequencies of dominant CD4 TCR clonotypes (0.1%–11% of all CD4 + T cells) remain stable post ART, suggesting that clonal homeostasis can be independent of homeostatic processes regulating CD4 + T cell absolute number, phenotypes, and function. The slow restoration of host immunity post ART also has implications for the design of ART interruption studies.

Source: Cell Reports Medicine

DOI: 10.1016/j.xcrm.2023.101268

Authors: Alexis Sponaugle, Ann Marie K. Weideman, Jolene Ranek, Gatphan Atassi, JoAnn Kuruc, Adaora A. Adimora, Nancie M. Archin, Cynthia Gay, Daniel R. Kuritzkes, David M. Margolis, Benjamin G. Vincent, Natalie Stanley, Michael G. Hudgens, Joseph J. Eron, Nilu Goonetilleke

Institutions: University of North Carolina at Chapel Hill, UNC Lineberger Comprehensive Cancer Center, Brigham and Women's Hospital, Harvard University

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $5,460

Funders: AIDS Clinical Trials Group, University of North Carolina, Harvard University, ACT Government, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Center for AIDS Research, University of North Carolina at Chapel Hill

Awards: G1079176756, G311558797, Phase I therapeutic testing of viral-vectored vaccines that shift CD8+ T cell immunodominance to conserved regions of HIV-1, G810223954, G9000033364, G9000240271, Gvl mHA Specific T Cell Responses Prevent AML Relapse Following Allogeneic Stem Cell Transplantation., AIDS Clinical Trial Group Laboratory Center, Collaboratory of AIDS Researchers for Eradication (CARE), Statistical and Data Management Center (SDMC), Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections (ACTG), The University of North Carolina Center for AIDS Research, University of North Carolina Global HIV Prevention and Treatment Clinical Trials Unit, Cancer Center Support Grant

OpenAlex ID: W4388540504

FWCI: 1.84

Cites: 136

Cited by: 14

Related to: 10