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Evaluation of Alloreactivity in Kidney Transplant Recipients Treated with Antithymocyte Globulin Versus IL‐2 Receptor Blocker
Author(s) -
Cherkassky L.,
Lanning M.,
Lalli P. N.,
Czerr J.,
Siegel H.,
DanzigerIsakov L.,
Srinivas T.,
Valujskikh A.,
Shoskes D. A.,
Baldwin W.,
Fairchild R. L.,
Poggio E. D.
Publication year - 2011
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2011.03540.x
Subject(s) - elispot , medicine , immunology , cd8 , flow cytometry , alloimmunity , t cell , kidney transplantation , transplantation , peripheral blood mononuclear cell , cytotoxic t cell , immune system , biology , in vitro , biochemistry
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.