title: Evaluation of alloreactivity in kidney transplant recipients treated with antithymocyte globulin versus IL-2 receptor blocker.
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.
authors.affiliation: Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: L
authors.initials: L
authors.lastname: Cherkassky
authors.forename: M
authors.initials: M
authors.lastname: Lanning
authors.forename: P N
authors.initials: PN
authors.lastname: Lalli
authors.forename: J
authors.initials: J
authors.lastname: Czerr
authors.forename: H
authors.initials: H
authors.lastname: Siegel
authors.forename: L
authors.initials: L
authors.lastname: Danziger-Isakov
authors.forename: T
authors.initials: T
authors.lastname: Srinivas
authors.forename: A
authors.initials: A
authors.lastname: Valujskikh
authors.forename: D A
authors.initials: DA
authors.lastname: Shoskes
authors.forename: W
authors.initials: W
authors.lastname: Baldwin
authors.forename: R L
authors.initials: RL
authors.lastname: Fairchild
authors.forename: E D
authors.initials: ED
authors.lastname: Poggio
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D000077552:Basiliximab; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D058501:Enzyme-Linked Immunospot Assay; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000961:Antilymphocyte Serum; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab