Mucosal associated invariant T cells are differentially impaired in tolerant and immunosuppressed liver transplant recipients.
T cell biology
basic (laboratory) research/science
flow cytometry
immunobiology
immunosuppressant
immunosuppression/immune modulation
liver transplantation/hepatology
lymphocyte biology: activation
tolerance
translational research/science
Journal
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
ISSN: 1600-6143
Titre abrégé: Am J Transplant
Pays: United States
ID NLM: 100968638
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
11
02
2020
revised:
12
05
2020
accepted:
26
05
2020
pubmed:
10
6
2020
medline:
22
6
2021
entrez:
10
6
2020
Statut:
ppublish
Résumé
Mucosal associated invariant T (MAIT-) cells represent a semi-invariant T cell population responsive to microbial vitamin B metabolite and innate cytokine stimulation, executing border tissue protection and particularly contributing to human liver immunity. The impact of immunosuppressants on MAIT cell biology alone and in context with solid organ transplantation has not been thoroughly examined. Here, we demonstrate that in vitro cytokine activation of peripheral MAIT cells from healthy individuals was impaired by glucocorticoids, whereas antigen-specific stimulation was additionally sensitive to calcineurin inhibitors. In liver transplant (LTx) recipients, significant depletion of peripheral MAIT cells was observed that was largely independent of the type and dosage of immunosuppression, equally applied to tolerant patients, and was reproducible in kidney transplant recipients. However, MAIT cells from tolerant LTx patients exhibited a markedly diminished ex vivo activation signature, associated with individual regain of functional competence toward antigenic and cytokine stimulation. Still, MAIT cells from tolerant and treated liver recipients exhibited high levels of PD1, accompanied by functional impairment particularly toward bacterial stimulation that also affected polyfunctionality. Our data suggest interlinked effects of primary liver pathology and immunosuppressive treatment on overall MAIT cell fitness after transplantation and propose their monitoring in context with tolerance induction protocols.
Identifiants
pubmed: 32515136
doi: 10.1111/ajt.16122
pii: S1600-6135(22)08320-4
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
87-102Informations de copyright
© 2020 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.
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