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Laetitia Gay, Marie-Sarah Rouviere, Soraya Mezouar, Manon Richaud, Laurent Gorvel, Etienne Foucher, Bernard La Scola, Amélie Menard, Jérôme Allardet-Servent, Philippe Halfon, Paul Frohna, Carla Cano, Jean-Louis Mege, Daniel Olive, Vγ9Vδ2 T-cells Are Potent Inhibitors of SARS-CoV-2 Replication and Represent Effector Phenotypes in Patients With COVID-19, The Journal of Infectious Diseases, Volume 229, Issue 6, 15 June 2024, Pages 1759–1769, https://doi.org/10.1093/infdis/jiae169
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Abstract
Vγ9Vδ2 T cells play a key role in the innate immune response to viral infections through butyrophilin 3A (BTN3A). Here, we report blood Vγ9Vδ2 T cells decreased in clinically mild COVID-19 compared to healthy volunteers, and this was maintained up to 28 days and in the recovery period. Terminally differentiated Vγ9Vδ2 T cells tended to be enriched on the day of diagnosis, 28 days after, and during the recovery period. These cells showed cytotoxic and inflammatory activities following anti-BTN3A activation. BTN3A upregulation and Vγ9Vδ2 T-cell infiltration were observed in a lung biopsy from a fatal SARS-CoV-2 infection. In vitro, SARS-CoV-2 infection increased BTN3A expression in macrophages and lung cells that enhanced the anti–SARS-CoV-2 Vγ9Vδ2 T-cell cytotoxicity and interferon-γ and tumor necrosis factor-α. Increasing concentrations of anti-BTN3A lead to viral replication inhibition. Altogether, we report Vγ9Vδ2 T cells are important in the immune response against SARS-CoV-2 infection and activation by anti-BTN3A antibody may enhance their response.
Clinical Trials Registration. NCT04816760.
![Graphical Abstract](https://cdn.statically.io/img/oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jid/229/6/10.1093_infdis_jiae169/1/m_jiae169_ga.jpeg?Expires=1724361020&Signature=BiKai4jjljmY1JmwSS9thpFBjZ-MN49gGLzh6WPN7cs0OYDy-Cv0I5F~zTgyuloOBJTTmm99nAZUJo0ORe55cu0l5zw7AfV6iYtxQ6aEnhGtxtkTwYjYmAKuVX9xYtqW-062BB7pRCP5yMnwv~WmcYduIY-YVYJ51gEOGPB1zgoEKDylzd3ka6qU7qTpJon7nonegSu~kufVk5MdeQZYlmzBgGtCKvhNAEMCYsFbhmE3CXyWG6Wby7tbkc18tmEWvd8YyEIlX8JAT9oviaKd0qLiTsy0etLpdFz2O2-ns0LLm33v12aQNPvGTOOLNUJghyRfNQK7bO8hPjXn-H1j5w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)