Unknown

Dataset Information

0

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


ABSTRACT: 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-IFN? 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.

SUBMITTER: Nakid-Cordero C 

PROVIDER: S-EPMC6804993 | BioStudies | 2019-01-01

REPOSITORIES: biostudies

Similar Datasets

2010-01-01 | S-EPMC2844307 | BioStudies
2017-01-01 | S-EPMC5498012 | BioStudies
1000-01-01 | S-EPMC6215901 | BioStudies
1000-01-01 | S-EPMC5067673 | BioStudies
2020-01-01 | S-EPMC7311655 | BioStudies
2019-01-01 | S-EPMC6769038 | BioStudies
1000-01-01 | S-EPMC5214975 | BioStudies
2015-01-01 | S-EPMC7172262 | BioStudies
1000-01-01 | S-EPMC5916001 | BioStudies
2019-01-01 | S-EPMC6366961 | BioStudies