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Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment in Kidney Transplant Recipients.

Publication ,  Journal Article
Xu, H; Samy, KP; Guasch, A; Mead, SI; Ghali, A; Mehta, A; Stempora, L; Kirk, AD
Published in: Am J Transplant
February 2016

Belatacept is used to prevent allograft rejection but fails to do so in a sizable minority of patients due to inadequate control of costimulation-resistant T cells. In this study, we report control of costimulation-resistant rejection when belatacept was combined with perioperative alemtuzumab-mediated lymphocyte depletion and rapamycin. To assess the means by which the alemtuzumab, belatacept and rapamycin (ABR) regimen controls belatacept-resistant rejection, we studied 20 ABR-treated patients and characterized peripheral lymphocyte phenotype and functional responses to donor, third-party and viral antigens using flow cytometry, intracellular cytokine staining and carboxyfluorescein succinimidyl ester-based lymphocyte proliferation. Compared with conventional immunosuppression in 10 patients, lymphocyte depletion evoked substantial homeostatic lymphocyte activation balanced by regulatory T and B cell phenotypes. The reconstituted T cell repertoire was enriched for CD28(+) naïve cells, notably diminished in belatacept-resistant CD28(-) memory subsets and depleted of polyfunctional donor-specific T cells but able to respond to third-party and latent herpes viruses. B cell responses were similarly favorable, without alloantibody development and a reduction in memory subsets-changes not seen in conventionally treated patients. The ABR regimen uniquely altered the immune profile, producing a repertoire enriched for CD28(+) T cells, hyporesponsive to donor alloantigen and competent in its protective immune capabilities. The resulting repertoire was permissive for control of rejection with belatacept monotherapy.

Duke Scholars

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

February 2016

Volume

16

Issue

2

Start / End Page

550 / 564

Location

United States

Related Subject Headings

  • Young Adult
  • Transplant Recipients
  • T-Lymphocytes, Regulatory
  • Surgery
  • Sirolimus
  • Risk Factors
  • Prognosis
  • Pilot Projects
  • Middle Aged
  • Male
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu, H., Samy, K. P., Guasch, A., Mead, S. I., Ghali, A., Mehta, A., … Kirk, A. D. (2016). Postdepletion Lymphocyte Reconstitution During Belatacept and Rapamycin Treatment in Kidney Transplant Recipients. Am J Transplant, 16(2), 550–564. https://doi.org/10.1111/ajt.13469
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

February 2016

Volume

16

Issue

2

Start / End Page

550 / 564

Location

United States

Related Subject Headings

  • Young Adult
  • Transplant Recipients
  • T-Lymphocytes, Regulatory
  • Surgery
  • Sirolimus
  • Risk Factors
  • Prognosis
  • Pilot Projects
  • Middle Aged
  • Male