Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients

Autor: Bidar, F., Hamada, S., Gossez, M., Coudereau, R., Lopez, J., Cazalis, M. A., Tardiveau, C., Brengel-Pesce, K., Mommert, M., Buisson, M., Conti, F., Rimmele, T., Lukaszewicz, A. C., Argaud, L., Cour, M., Monneret, G., Venet, F.
Přispěvatelé: Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Lyon (ENS Lyon), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre d'Investigation Clinique [Bron] (CIC1407), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupement Hospitalier Est [Bron], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), RICO Study Group: Remi Pescarmona, Lorna Garnier, Christine Lombard, Magali Perret, Marine Villard, Sébastien Viel, Valérie Cheynet, Elisabeth Cerrato, Estelle Peronnet, Jean-François Llitjos, Laetitia Itah, Inesse Boussaha, Françoise Poitevin-Later, Christophe Malcus, Marine Godignon, Florent Wallet, Marie-Charlotte Delignette, Frederic Dailler, Marie Simon, Auguste Dargent, Pierre-Jean Bertrand, Neven Stevic, Marion Provent, Laurie Bignet, Valérie Cerro, Jean-Christophe Richard, Laurent Bitker, Mehdi Mezidi, Loredana Baboi., CarMeN, laboratoire, Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Annals of Intensive Care
Annals of Intensive Care, 2022, 12 (1), pp.21. ⟨10.1186/s13613-022-00982-1⟩
ISSN: 2110-5820
DOI: 10.1186/s13613-022-00982-1⟩
Popis: Erratum inCorrection to: Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients.Bidar F, Hamada S, Gossez M, Coudereau R, Lopez J, Cazalis MA, Tardiveau C, Brengel-Pesce K, Mommert M, Buisson M, Conti F, Rimmelé T, Lukaszewicz AC, Argaud L, Cour M, Monneret G, Venet F; RICO Study Group.Ann Intensive Care. 2022 Apr 1;12(1):30. doi: 10.1186/s13613-022-01007-7.; International audience; BACKGROUND: Lymphopenia is a hallmark of severe coronavirus disease 19 (COVID-19). Similar alterations have been described in bacterial sepsis and therapeutic strategies targeting T cell function such as recombinant human interleukin 7 (rhIL-7) have been proposed in this clinical context. As COVID-19 is a viral sepsis, the objectives of this study were to characterize T lymphocyte response over time in severe COVID-19 patients and to assess the effect of ex vivo administration of rhIL-7. RESULTS: Peripheral blood mononuclear cells from COVID-19 patients hospitalized in intensive care unit (ICU) were collected at admission and after 20 days. Transcriptomic profile was evaluated through NanoString technology. Inhibitory immune checkpoints expressions were determined by flow cytometry. T lymphocyte proliferation and IFN-γ production were evaluated after ex vivo stimulation in the presence or not of rhIL-7. COVID-19 ICU patients were markedly lymphopenic at admission. Mononuclear cells presented with inhibited transcriptomic profile prevalently with impaired T cell activation pathways. CD4 + and CD8 + T cells presented with over-expression of co-inhibitory molecules PD-1, PD-L1, CTLA-4 and TIM-3. CD4 + and CD8 + T cell proliferation and IFN-γ production were markedly altered in samples collected at ICU admission. These alterations, characteristic of a T cell exhaustion state, were more pronounced at ICU admission and alleviated over time. Treatment with rhIL-7 ex vivo significantly improved both T cell proliferation and IFN-γ production in cells from COVID-19 patients. CONCLUSIONS: Severe COVID-19 patients present with features of profound T cell exhaustion upon ICU admission which can be reversed ex vivo by rhIL-7. These results reinforce our understanding of severe COVID-19 pathophysiology and opens novel therapeutic avenues to treat such critically ill patients based of immunomodulation approaches. Defining the appropriate timing for initiating such immune-adjuvant therapy in clinical setting and the pertinent markers for a careful selection of patients are now warranted to confirm the ex vivo results described so far. Trial registration ClinicalTrials.gov identifier: NCT04392401 Registered 18 May 2020, http:// clinicaltrials.gov/ct2/show/NCT04392401.
Databáze: OpenAIRE
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