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

Publication ,  Journal Article
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 in: Am J Transplant
April 2016

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.

Duke Scholars

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

April 2016

Volume

16

Issue

4

Start / End Page

1102 / 1112

Location

United States

Related Subject Headings

  • Surgery
  • Risk Factors
  • Prognosis
  • Polymerase Chain Reaction
  • Oligonucleotide Array Sequence Analysis
  • Kidney Transplantation
  • Kidney Function Tests
  • Kidney Failure, Chronic
  • Immunosuppressive Agents
  • Immunologic Memory
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Espinosa, J., Herr, F., Tharp, G., Bosinger, S., Song, M., Farris, A. B., … Kirk, A. D. (2016). CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection. Am J Transplant, 16(4), 1102–1112. https://doi.org/10.1111/ajt.13613
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

April 2016

Volume

16

Issue

4

Start / End Page

1102 / 1112

Location

United States

Related Subject Headings

  • Surgery
  • Risk Factors
  • Prognosis
  • Polymerase Chain Reaction
  • Oligonucleotide Array Sequence Analysis
  • Kidney Transplantation
  • Kidney Function Tests
  • Kidney Failure, Chronic
  • Immunosuppressive Agents
  • Immunologic Memory