Immune mobilising T cell receptors redirect polyclonal CD8 + T cells in chronic HIV infection to form immunological synapses.

Autor: Wallace Z; Nuffield Department of Medicine, University of Oxford, Oxford, UK. zoe.wallace@immunocore.com.; Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK. zoe.wallace@immunocore.com.; Immunocore Ltd, 92 Park Drive, Abingdon, Oxfordshire, UK. zoe.wallace@immunocore.com., Kopycinski J; Nuffield Department of Medicine, University of Oxford, Oxford, UK., Yang H; Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK., McCully ML; Immunocore Ltd, 92 Park Drive, Abingdon, Oxfordshire, UK., Eggeling C; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.; Leibniz Institute of Photonic Technology & Institute of Applied Optics and Biophysics, Friedrich-Schiller University, Jena, Germany., Chojnacki J; MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Dorrell L; Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK.; Immunocore Ltd, 92 Park Drive, Abingdon, Oxfordshire, UK.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Nov 01; Vol. 12 (1), pp. 18366. Date of Electronic Publication: 2022 Nov 01.
DOI: 10.1038/s41598-022-23228-3
Abstrakt: T cell exhaustion develops in human immunodeficiency virus (HIV) infection due to chronic viral antigenic stimulation. This adaptive response primarily affects virus-specific CD8 + T cells, which may remain dysfunctional despite viral load-reducing antiretroviral therapy; however, abnormalities may also be evident in non-HIV-specific populations. Both could limit the efficacy of cell therapies against viral reservoirs. Here, we show that bulk (polyclonal) CD8 + T cells from people living with HIV (PLWH) express proposed markers of dysfunctional HIV-specific T cells at high levels yet form lytic immunological synapses (IS) and eliminate primary resting infected (HIV Gag lo ) CD4 + T cells, when redirected by potent bispecific T cell-retargeting molecules, Immune mobilising monoclonal T cell receptors (TCR) Against Virus (ImmTAV). While PLWH CD8 + T cells are functionally impaired when compared to CD8 + T cells from HIV-naïve donors, ImmTAV redirection enables them to eliminate Gag lo CD4 + T cells that are insensitive to autologous HIV-specific cytolytic T cells. ImmTAV molecules may therefore be able to target HIV reservoirs, which represent a major barrier to a cure.
(© 2022. The Author(s).)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje