Chronic inflammation degrades CD4 T cell immunity to prior vaccines in treated HIV infection

Kießling M, Cole JJ, Kübel S, Klein P, Korn K, Henry AR, Laboune F, Fourati S, Harrer E, Harrer T, Douek DC, Überla K, Nganou-Makamdop K (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 15

Article Number: 10200

Journal Issue: 1

DOI: 10.1038/s41467-024-54605-3

Abstract

To date, our understanding of how HIV infection impacts vaccine-induced cellular immunity is limited. Here, we investigate inflammation, immune activation and antigen-specific T cell responses in HIV-uninfected and antiretroviral-treated HIV-infected people. Our findings highlight lower recall responses of antigen-specific CD4 T cells that correlate with high plasma cytokines levels, T cell hyperactivation and an altered composition of the T subsets enriched with more differentiated cells in the HIV-infected group. Transcriptomic analysis reveals that antigen-specific CD4 T cells of the HIV-infected group have a reduced expression of gene sets previously reported to correlate with vaccine-induced pathogen-specific protective immunity and further identifies a consistent impairment of the IFNα and IFNγ response pathways as mechanism for the functional loss of recall CD4 T cell responses in antiretroviral-treated people. Lastly, in vitro treatment with drugs that reduce inflammation results in higher memory CD4 T cell IFNγ responses. Together, our findings suggest that vaccine-induced cellular immunity may benefit from strategies to counteract inflammation in HIV infection.

Authors with CRIS profile

Melissa Kießling Institute of Clinical and Molecular Virology Sabrina Kübel Lehrstuhl für Klinische und Molekulare Virologie Paulina Klein Institute of Clinical and Molecular Virology Klaus Korn Institute of Clinical and Molecular Virology Ellen Harrer Department of Medicine 3 – Rheumatology and Immunology Thomas Harrer Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz Klaus Überla Lehrstuhl für Klinische und Molekulare Virologie Christiane Krystelle Nganou Makamdop Institute of Clinical and Molecular Virology

Involved external institutions

US National Institutes of Health (NIH) US United States (USA) (US) Northwestern University US United States (USA) (US) University of Glasgow GB United Kingdom (GB)

How to cite

APA:

Kießling, M., Cole, J.J., Kübel, S., Klein, P., Korn, K., Henry, A.R.,... Nganou-Makamdop, K. (2024). Chronic inflammation degrades CD4 T cell immunity to prior vaccines in treated HIV infection. Nature Communications, 15(1). https://doi.org/10.1038/s41467-024-54605-3

MLA:

Kießling, Melissa, et al. "Chronic inflammation degrades CD4 T cell immunity to prior vaccines in treated HIV infection." Nature Communications 15.1 (2024).

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