Skewed T cell responses to Epstein-Barr virus in long-term asymptomatic kidney transplant recipients


Autoři: Cecilia Nakid-Cordero aff001;  Nadia Arzouk aff002;  Nicolas Gauthier aff001;  Nadine Tarantino aff001;  Martin Larsen aff001;  Sylvain Choquet aff001;  Sonia Burrel aff001;  Brigitte Autran aff001;  Vincent Vieillard aff001;  Amélie Guihot aff001
Působiště autorů: Sorbonne Université (Univ. Paris 06), INSERM U1135, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Hôpital Pitié-Salpêtrière, Paris, France aff001;  Service de Néphrologie, Urologie et Transplantation Rénale, Hôpital Pitié Salpêtrière, Paris, France aff002;  CNRS ERL8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France aff003;  Service d’Hématologie, Hôpital Pitié Salpêtrière, Paris, France aff004;  Service de Virologie, Hôpital Pitié Salpêtrière, Paris, France aff005;  Département d’Immunologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Pitié-Salpêtrière, Paris, France aff006
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224211

Souhrn

Kidney transplant recipients (KTRs) abnormally replicate the Epstein Barr Virus (EBV). To better understand how long-term immunosuppression impacts the immune control of this EBV re-emergence, we systematically compared 10 clinically stable KTRs to 30 healthy controls (HCs). The EBV-specific T cell responses were determined in both groups by multiparameter flow cytometry with intra cellular cytokine staining (KTRs n = 10; HCs n = 15) and ELISpot-IFNγ assays (KTRs n = 7; HCs n = 7). The T/B/NK cell counts (KTRs n = 10; HCs n = 30) and the NK/T cell differentiation and activation phenotypes (KTRs n = 10; HCs n = 15/30) were also measured. We show that in KTRs, the Th1 effector CD4+ T cell responses against latent EBV proteins are weak (2/7 responders). Conversely, the frequencies total EBV-specific CD8+T cells are conserved in KTRs (n = 10) and span a wider range of EBNA-3A peptides (5/7responders) than in HCs (5/7responders). Those modifications of the EBV-specific T cell response were associated with a profound CD4+ T cell lymphopenia in KTRs compared to HCs, involving the naïve CD4+ T cell subset, and a persistent activation of highly-differentiated senescent CD8+ T cells. The proportion of total NK / CD8+ T cells expressing PD-1 was also increased in KTRs. Noteworthy, PD-1 expression on CD8+ T cells normalized with time after transplantation. In conclusion, we show modifications of the EBV-specific cellular immunity in long term transplant recipients. This may be the result of both persistent EBV antigenic stimulation and profound immunosuppression induced by anti-rejection treatments. These findings provide new insights into the immunopathology of EBV infection after renal transplantation.

Klíčová slova:

Cytokines – Cytotoxic T cells – Epstein-Barr virus – Flow cytometry – Immune response – NK cells – Renal transplantation – T cells


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2019 Číslo 10