Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker

L. Cherkassky, M. Lanning, P. N. Lalli, J. Czerr, H. Siegel, L. Danziger-Isakov, T. Srinivas, A. Valujskikh, D. A. Shoskes, W. Baldwin, R. L. Fairchild, E. D. Poggio

Research output: Contribution to journalArticlepeer-review

Abstract

Induction therapy is used in kidney transplantation to inhibit the activation of donor-reactive T cells which are detrimental to transplant outcomes. The choice of induction therapy is decided based on perceived immunological risk rather than by direct measurement of donor T-cell reactivity. We hypothesized that immune cellular alloreactivity pretransplantation can be quantified and that blocking versus depleting therapies have differential effects on the level of donor and third-party cellular alloreactivity. We studied 31 kidney transplant recipients treated with either antithymocyte globulin (ATG) or an IL-2 receptor blocker. We tested pre- and posttransplant peripheral blood cells by flow cytometry to characterize T-cell populations and by IFN-γ ELISPOT assays to assess the level of cellular alloreactivity. CD8 + T cells were more resistant to depletion by ATG than CD4 + T cells. Posttransplantation, frequencies of donor-reactive T cells were markedly decreased in the ATG-treated group but not in the IL-2 receptor blocker group, whereas the frequencies of third-party alloreactivity remained nearly equivalent. In conclusion, when ATG is used, marked and prolonged donor hyporesponsiveness with minimal effects on nondonor responses is observed. In contrast, induction with the IL-2 receptor blocker is less effective at diminishing donor T-cell reactivity.

Original languageEnglish (US)
Pages (from-to)1388-1396
Number of pages9
JournalAmerican Journal of Transplantation
Volume11
Issue number7
DOIs
StatePublished - Jul 2011
Externally publishedYes

Keywords

  • Donor immunity
  • ELISPOT
  • induction
  • T-cell
  • thymoglobulin

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

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