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IL-7 receptor heterogeneity as a mechanism for repertoire change during postdepletional homeostatic proliferation and its relation to costimulation blockade-resistant rejection.

Publication ,  Journal Article
Xu, H; Bendersky, VA; Brennan, TV; Espinosa, JR; Kirk, AD
Published in: Am J Transplant
March 2018

Kidney transplant patients treated with belatacept without depletional induction experience higher rates of acute rejection compared to patients treated with conventional immunosuppression. Costimulation blockade-resistant rejection (CoBRR) is associated with terminally differentiated T cells. Alemtuzumab induction and belatacept/sirolimus immunotherapy effectively prevent CoBRR. We hypothesized that cells in late phases of differentiation would be selectively less capable than more naive phenotypes of repopulating postdepletion, providing a potential mechanism by which lymphocyte depletion and repopulation could reduce the risk of CoBRR. Lymphocytes from 20 recipients undergoing alemtuzumab-induced depletion and belatacept/sirolimus immunosuppression were studied longitudinally for markers of maturation (CCR7, CD45RA, CD57, PD1), recent thymic emigration (CD31), and the IL-7 receptor-α (IL-7Rα). Serum was analyzed for IL-7. Alemtuzumab induction produced profound lymphopenia followed by repopulation, during which naive IL-7Rα+ CD57- PD1- cells progressively became the predominant subset. This did not occur in a comparator group of 10 patients treated with conventional immunosuppression. Serum from depleted patients showed markedly elevated IL-7 levels posttransplantation. Sorted CD57- PD1- cells demonstrated robust proliferation in response to IL-7, whereas more differentiated cells proliferated poorly. These data suggest that differences in IL-7-dependent proliferation is one exploitable mechanism that distinguishes CoB-sensitive and CoB-resistant T cell populations to reduce the risk of CoBRR. (ClinicalTrials.gov - NCT00565773.).

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Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

March 2018

Volume

18

Issue

3

Start / End Page

720 / 730

Location

United States

Related Subject Headings

  • Surgery
  • Risk Factors
  • Receptors, Interleukin-7
  • Prognosis
  • Lymphocyte Depletion
  • Kidney Transplantation
  • Interleukin-7
  • Immunosuppressive Agents
  • Immunologic Memory
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu, H., Bendersky, V. A., Brennan, T. V., Espinosa, J. R., & Kirk, A. D. (2018). IL-7 receptor heterogeneity as a mechanism for repertoire change during postdepletional homeostatic proliferation and its relation to costimulation blockade-resistant rejection. Am J Transplant, 18(3), 720–730. https://doi.org/10.1111/ajt.14589
Xu, He, Victoria A. Bendersky, Todd V. Brennan, Jaclyn R. Espinosa, and Allan D. Kirk. “IL-7 receptor heterogeneity as a mechanism for repertoire change during postdepletional homeostatic proliferation and its relation to costimulation blockade-resistant rejection.Am J Transplant 18, no. 3 (March 2018): 720–30. https://doi.org/10.1111/ajt.14589.
Journal cover image

Published In

Am J Transplant

DOI

EISSN

1600-6143

Publication Date

March 2018

Volume

18

Issue

3

Start / End Page

720 / 730

Location

United States

Related Subject Headings

  • Surgery
  • Risk Factors
  • Receptors, Interleukin-7
  • Prognosis
  • Lymphocyte Depletion
  • Kidney Transplantation
  • Interleukin-7
  • Immunosuppressive Agents
  • Immunologic Memory
  • Humans