CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.
Journal Article (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
- PMC4867077
Electronic International Standard Serial Number (EISSN)
- 1600-6143
Digital Object Identifier (DOI)
- 10.1111/ajt.13613
Language
- eng
Conference Location
- United States