Chronic lung allograft dysfunction is associated with an early increase of circulating cytotoxic CD4+CD57+ILT2+ T cells, selectively inhibited by the immune check-point HLA-G.

Autor:	Brugière O; Service de Pneumologie et Transplantation Pulmonaire, Hôpital Foch, Suresnes, France; CEA, DRF-Institut François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France; U976 HIPI Unit, IRSL, Université Paris, Paris, France. Electronic address: o.brugiere@hopital-foch.com., Mouren D; CEA, DRF-Institut François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France; U976 HIPI Unit, IRSL, Université Paris, Paris, France., Trichereau J; Département de biostatistiques, DRCI Hôpital Foch, Suresnes, France., Vallée A; Département de biostatistiques, DRCI Hôpital Foch, Suresnes, France., Kuzniak I; CEA, DRF-Institut François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France; U976 HIPI Unit, IRSL, Université Paris, Paris, France., Hirschi S; Service de Pneumologie et Transplantation Pulmonaire, CHU de Strasbourg, France., Renaud-Picard B; Service de Pneumologie et Transplantation Pulmonaire, CHU de Strasbourg, France., Reynaud-Gaubert M; Service de Pneumologie et Transplantation Pulmonaire, CHU de Marseille, France., Nieves A; Service de Pneumologie et Transplantation Pulmonaire, CHU de Marseille, France., Bunel V; Service de Pneumologie et Transplantation Pulmonaire, Hôpital Bichat, Paris, France., Messika J; Service de Pneumologie et Transplantation Pulmonaire, Hôpital Bichat, Paris, France., Demant X; Service de Pneumologie et Transplantation Pulmonaire, CHU de Bordeaux, France., Macey J; Service de Pneumologie et Transplantation Pulmonaire, CHU de Bordeaux, France., Le Pavec J; Service de Pneumologie et Transplantation Pulmonaire, hôpital Marie-Lannelongue, Le plessis-Robisson, France., Dauriat G; Service de Pneumologie et Transplantation Pulmonaire, hôpital Marie-Lannelongue, Le plessis-Robisson, France., Saint-Raymond C; Service de Pneumologie et Transplantation Pulmonaire, CHU de Grenoble, France., Falque L; Service de Pneumologie et Transplantation Pulmonaire, CHU de Grenoble, France., Mornex JF; Service de Pneumologie et Transplantation Pulmonaire, CHU de Lyon, France., Tissot A; Service de Pneumologie et Transplantation Pulmonaire, CHU de Nantes, France., Foureau A; Service de Pneumologie et Transplantation Pulmonaire, CHU de Nantes, France., Borgne Krams AL; Service de Pneumologie et Transplantation Pulmonaire, CHU de Toulouse, France., Bousseau V; Service de Pneumologie et Transplantation Pulmonaire, Hôpital HEGP, Paris, France., Magnan A; Service de Pneumologie et Transplantation Pulmonaire, Hôpital Foch, Suresnes, France., Picard C; Service de Pneumologie et Transplantation Pulmonaire, Hôpital Foch, Suresnes, France., Roux A; Service de Pneumologie et Transplantation Pulmonaire, Hôpital Foch, Suresnes, France., Carosella E; CEA, DRF-Institut François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France; U976 HIPI Unit, IRSL, Université Paris, Paris, France., LeMaoult J; CEA, DRF-Institut François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France; U976 HIPI Unit, IRSL, Université Paris, Paris, France., Rouas-Freiss N; CEA, DRF-Institut François Jacob, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France; U976 HIPI Unit, IRSL, Université Paris, Paris, France.
Jazyk:	angličtina
Zdroj:	The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2022 May; Vol. 41 (5), pp. 626-640. Date of Electronic Publication: 2022 Jan 24.
DOI:	10.1016/j.healun.2022.01.013
Abstrakt:	Background: Survival after lung transplantation (LTx) still remains limited by chronic lung allograft dysfunction (CLAD), thought to represent a form of chronic rejection. We investigated whether the immune checkpoint HLA-G/ILT2 expressed by peripheral T-cell subpopulations could predict CLAD. Methods: We used data for 150 LTx recipients from COLT (Cohort-For-Lung-Transplantation) cohort with ≥1 available blood sample at 1-, 6-, or 12-months post-Tx. Analysis of T cells by flow cytometry focused on the ILT2 receptor of HLA-G and other markers (CD57, CD25, CD127). T-cell subset analyses compared stable patients and those with CLAD at 3 years post-LTx. Results: With data for 78 stable and 72 CLAD patients, among 21 T-cell subsets expressing ILT2, only CD4+CD57+ILT2+ T cells were associated with outcome. At 1-month post-Tx, low proportion of CD4+CD57+ILT2+ T cells was associated with reduced 3-year incidence of CLAD (CD4+CD57+ILT2+ T cells ≤ first IQR [25%] vs > first IQR, log-rank test, p = 0.028). Furthermore, the incidence of CLAD was higher with >2.6- vs ≤2.6-fold increased proportion of CD4+CD57+ILT2+ T cells over the first year post-LTx (3-year freedom frequencies: 27% [95%CI: 8-50] vs 64% [95%CI: 48-77] (log-rank test, p = 0.014). On multivariable analysis, increased proportion of CD4+CD57+ILT2+ T cells over the first year predicted CLAD (hazard ratio 1.25; 95%CI: 1.09-1.44; p = 0.001). Focusing on CD4+CD57+ILT2+ T cells, we demonstrated ex vivo that they are cytotoxic CD4+ T cells, selectively inhibited by HLA-G. Conclusions: Our data suggest that an early increase of CD4+CD57+ILT2+ T cells after LTx may be associated with CLAD onset. Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose. (Copyright © 2022. Published by Elsevier Inc.)
Databáze:	MEDLINE
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