High circulating CD4+CD25hiFOXP3+T-cell sub-population early after lung transplantation is associated with development of bronchiolitis obliterans syndrome

Maxim Durand (1) , Philippe Lacoste (2) , Richard Danger (3, 1) , Lola Jacquemont (3, 1) , Carole Brosseau (1) , Eugénie Durand (1) , Gaelle Tilly (3, 1) , Jennifer Loy (2) , Aurore Foureau (2) , Pierre-Joseph Royer (2) , Adrien Tissot (2, 4) , Antoine Roux (5) , Martine Reynaud-Gaubert (6) , Romain Kessler (7) , Sacha Mussot (8) , Claire Dromer (9) , Olivier Brugière (10) , Jean François Mornex (11) , Romain Guillemain (12) , Johanna Claustre (13) , Nicolas Degauque (3, 1) , Antoine Magnan (2) , Sophie Brouard (3, 1)

1 Team 4 - U1064 Inserm - CRTI - Immunoregulation And Immunointervention in Transplantation and Autoimmunity
2 ITX - ITX - unité de recherche de l'institut du thorax
3 ITUN - Institut de transplantation urologie-néphrologie
4 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
5 LOBIP - Laboratoire de recherche sur les mécanismes moléculaires et pharmacologiques de l’obstruction bronchique
6 MEPHI - Microbes évolution phylogénie et infections
7 Service de Pneumologie
8 Service de Chirurgie Thoracique, Vasculaire et Transplantation Cardiopulmonaire
9 Service Maladies Respiratoires
10 Service de pneumologie B
11 HCL - Hospices Civils de Lyon
12 Department of Chest Medicine
13 Clinique Universitaire de Pneumologie, Pôle Thorax et Vaisseaux

BACKGROUND: Chronic bronchiolitis obliterans syndrome (BOS) remains a major limitation for long-term survival after lung transplantation. The immune mechanisms involved and predictive biomarkers have yet to be identified. The purpose of this study was to determine whether peripheral blood T-lymphocyte profile could predict BOS in lung transplant recipients.

METHODS: An in-depth profiling of CD4+and CD8+T cells was prospectively performed on blood cells from stable (STA) and BOS patients with a longitudinal follow-up. Samples were analyzed at 1 and 6 months after transplantation, at the time of BOS diagnosis, and at an intermediate time-point at 6 to 12 months before BOS diagnosis.

RESULTS: Although no significant difference was found for T-cell compartments at BOS diagnosis or several months beforehand, we identified an increase in the CD4+CD25hiFoxP3+T-cell sub-population in BOS patients at 1 and 6 months after transplantation (3.39 ± 0.40% vs 1.67 ± 0.22% in STA, p \textless 0.001). A CD4+CD25hiFoxP3+T-cell threshold of 2.4% discriminated BOS and stable patients at 1 month post-transplantation. This was validated on a second set of patients at 6 months post-transplantation. Patients with a proportion of CD4+CD25hiFoxP3+T cells up to 2.4% in the 6 months after transplantation had a 2-fold higher risk of developing BOS.

CONCLUSIONS: This study is the first to report an increased proportion of circulating CD4+CD25hiFoxP3+T cells early post-transplantation in lung recipients who proceed to develop BOS within 3 years, which supports its use as a BOS predictive biomarker.

Mots clés: regulatory T lymphocyte; biomarker; bronchiolitis obliterans syndrome; chronic lung allograft dysfunction; T lymphocyte

Domaines: Sciences du Vivant [q-bio]

Maxim Durand, Philippe Lacoste, Richard Danger, Lola Jacquemont, Carole Brosseau, et al.. High circulating CD4+CD25hiFOXP3+T-cell sub-population early after lung transplantation is associated with development of bronchiolitis obliterans syndrome. The Journal of Heart and Lung Transplantation, 2018, Equipe III, 37 (6), pp.770-781. ⟨10.1016/j.healun.2018.01.1306⟩. ⟨hal-01833919⟩