HIV-1-Specific Chimeric Antigen Receptor T Cells Fail To Recognize and Eliminate the Follicular Dendritic Cell HIV Reservoir In Vitro

Author:

Ollerton Matthew T.1,Berger Edward A.2,Connick Elizabeth3,Burton Gregory F.1

Affiliation:

1. Department of Chemistry and Biochemistry, Brigham Young University, Provo, Utah, USA

2. Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

3. Department of Medicine, University of Arizona, Tucson, Arizona, USA

Abstract

Efforts to cure HIV infection have focused primarily on the elimination of latently infected CD4 + T cells. Few studies have addressed the unique reservoir of infectious HIV that exists on follicular dendritic cells (FDCs), persists in vivo during antiretroviral therapy, and likely contributes to viral rebound upon cessation of antiretroviral therapy. We assessed the efficacy of a novel HIV-specific chimeric antigen receptor (CAR) T cell to target both HIV-infected CD4 + T cells and the FDC reservoir in vitro . Although CAR-T cells eliminated CD4 + T cells that express HIV, they did not respond to or eliminate FDC bound to HIV. These findings reveal a fundamental limitation to CAR-T cell therapy to eradicate HIV.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Brigham Young University

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference47 articles.

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2. Targeting the Latent Reservoir for HIV-1

3. Follicular dendritic cells retain HIV-1 particles on their plasma membrane, but are not productively infected in asymptomatic patients with follicular hyperplasia;Schmitz J;J Immunol,1994

4. Characterization of the Follicular Dendritic Cell Reservoir of Human Immunodeficiency Virus Type 1

5. Persistence of Infectious HIV on Follicular Dendritic Cells

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