CD57+ CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection

J. Espinosa, F. Herr, G. Tharp, S. Bosinger, M. Song, A. B. Farris, R. George, J. Cheeseman, L. Stempora, R. Townsend, A. Durrbach, A. D. Kirk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

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 (CoBRR), but this remains undefined in humans. To explore relationships between individual patients' immune cell phenotypes and CoBRR, we studied patients receiving belatacept or conventional calcineurin inhibitor-based immunosuppression. We identified a population of CD57+PD1- CD4 T cells present prior to transplantation that correlated with CoBRR. Contrary to data recognizing CD57 as a marker of senescence on CD8 T cells, we discovered a nonsenescent, cytolytic phenotype associated with CD57 on CD4 T cells. Moreover, CD57+ CD4 T cells expressed high levels of adhesion molecules implicated in experimental CoBRR, were CD28-, expressed a transcriptional phenotype broadly defining allograft rejection and were shown to be present in rejecting human kidney allografts. These data implicate CD57+ CD4 T cells in clinical CoBRR. If prospectively validated, this characteristic could identify patients at higher risk for acute rejection on belatacept-based therapy.

Original languageEnglish
Pages (from-to)1102-1112
Number of pages11
JournalAmerican Journal of Transplantation
Volume16
Issue number4
DOIs
StatePublished - 1 Apr 2016
Externally publishedYes

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