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CD 57 + CD 4 T Cells Underlie Belatacept‐Resistant Allograft Rejection
Author(s) -
Espinosa J.,
Herr F.,
Tharp G.,
Bosinger S.,
Song M.,
Farris A. B.,
George R.,
Cheeseman J.,
Stempora L.,
Townsend R.,
Durrbach A.,
Kirk A. D.
Publication year - 2016
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.13613
Subject(s) - belatacept , calcineurin , cd28 , immunosuppression , medicine , immunology , t cell , immune system , population , cd8 , abatacept , cancer research , transplantation , kidney transplantation , antibody , kidney transplant , rituximab , environmental health
Belatacept is a B7‐specific fusion protein used to prevent allograft rejection by blocking T cell costimulation. Generally efficacious, it fails to prevent acute rejection in a sizable minority of patients. In experimental models, memory T cells mediate costimulation blockade–resistant rejection (Co BRR ), but this remains undefined in humans. To explore relationships between individual patients' immune cell phenotypes and Co BRR , we studied patients receiving belatacept or conventional calcineurin inhibitor–based immunosuppression. We identified a population of CD 57 + PD 1 − CD 4 T cells present prior to transplantation that correlated with Co BRR . Contrary to data recognizing CD 57 as a marker of senescence on CD 8 T cells, we discovered a nonsenescent, cytolytic phenotype associated with CD 57 on CD 4 T cells. Moreover, CD 57 + CD 4 T cells expressed high levels of adhesion molecules implicated in experimental Co BRR, were CD 28 − , expressed a transcriptional phenotype broadly defining allograft rejection and were shown to be present in rejecting human kidney allografts. These data implicate CD 57 + CD 4 T cells in clinical Co BRR . If prospectively validated, this characteristic could identify patients at higher risk for acute rejection on belatacept‐based therapy.