Activated CD4 + T Cells and Highly Differentiated Alloreactive CD4 + T Cells Distinguish Operationally Tolerant Liver Transplantation Recipients.

Autor: Duizendstra AA; Department of Gastroenterology and Hepatology Erasmus MC University Medical Center Rotterdam the Netherlands Erasmus MC Transplant Institute, Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam the Netherlands Department of Immunohematology and Blood Transfusion Leiden University Medical Center Leiden the Netherlands Department of Pathology Erasmus MC University Medical Center Rotterdam the Netherlands., de Knegt RJ, Mancham S, Klepper M, Roelen DL, Brand-Schaaf SH, Boor PP, Doukas M, de Man RA, Sprengers D, Peppelenbosch MP, Betjes MGH, Kwekkeboom J, Litjens NHR
Jazyk: angličtina
Zdroj: Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society [Liver Transpl] 2022 Jan; Vol. 28 (1), pp. 98-112. Date of Electronic Publication: 2021 Jul 21.
DOI: 10.1002/lt.26188
Abstrakt: Spontaneous operational tolerance to the allograft develops in a proportion of liver transplantation (LT) recipients weaned off immunosuppressive (IS) drugs. Several studies have investigated whether peripheral blood circulating T cells could play a role in the development or identify operational tolerance, but never characterized alloreactive T cells in detail due to the lack of a marker for these T cells. In this study, we comprehensively investigated phenotypic and functional characteristics of alloreactive circulating T cell subsets in tolerant LT recipients (n = 15) using multiparameter flow cytometry and compared these with LT recipients on IS drugs (n = 23) and healthy individuals (n = 16). Activation-induced CD137 was used as a marker for alloreactive T cells upon allogenic stimulation. We found that central and effector memory CD4+ T cells were hyporesponsive against donor and third-party splenocyte stimulation in tolerant LT recipients, whereas an overall hyperresponsiveness was observed in alloreactive terminally differentiated effector memory CD4+ T cells. In addition, elevated percentages of circulating activated T helper cells were observed in these recipients. Lastly, tolerant and control LT recipients did not differ in donor-specific antibody formation. In conclusion, a combination of circulating hyperresponsive highly differentiated alloreactive CD4+ T cells and circulating activated T helper cells could discriminate tolerant recipients from a larger group of LT recipients.
(Copyright © 2021 The Authors. Liver Transplantation published by Wiley Periodicals LLC on behalf of American Association for the Study of Liver Diseases.)
Databáze: MEDLINE
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