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Activated CD4 + T Cells and Highly Differentiated Alloreactive CD4 + T Cells Distinguish Operationally Tolerant Liver Transplantation Recipients
Author(s) -
Duizendstra Aafke A.,
Knegt Robert J.,
Mancham Shanta,
Klepper Mariska,
Roelen Dave L.,
BrandSchaaf Simone H.,
Boor Patrick P.,
Doukas Michail,
Man Robert A.,
Sprengers Dave,
Peppelenbosch Maikel P.,
Betjes Michiel G. H.,
Kwekkeboom Jaap,
Litjens Nicolle H. R.
Publication year - 2022
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.26188
Subject(s) - cd137 , immunology , medicine , flow cytometry , transplantation , effector , liver transplantation , splenocyte , stimulation , t cell , antibody , immune system
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.