CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Espinosa, J; Herr, F; Tharp, G; Bosinger, S; Song, M; Farris, AB; George, R; Cheeseman, J; Stempora, L; Townsend, R; Durrbach, A; Kirk, AD

Published Date

  • April 2016

Published In

Volume / Issue

  • 16 / 4

Start / End Page

  • 1102 - 1112

PubMed ID

  • 26603381

Pubmed Central ID

  • 26603381

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

International Standard Serial Number (ISSN)

  • 1600-6135

Digital Object Identifier (DOI)

  • 10.1111/ajt.13613

Language

  • eng