Evaluation of Alloreactivity in Kidney Transplant Recipients Treated with Antithymocyte Globulin Versus IL‐2 Receptor Blocker

• Published in: American journal of transplantation Vol. 11; no. 7; pp. 1388 - 1396
• Main Authors: Cherkassky, L., Lanning, M., Lalli, P. N., Czerr, J., Siegel, H., Danziger‐Isakov, L., Srinivas, T., Valujskikh, A., Shoskes, D. A., Baldwin, W., Fairchild, R. L., Poggio, E. D.
• Format: Journal Article
• Language: English
• Published: Malden, USA Blackwell Publishing Inc 01-07-2011; Wiley
• Subjects: Antibodies, Monoclonal - therapeutic use; Antilymphocyte Serum - therapeutic use; Basiliximab; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - drug effects; Donor immunity; ELISPOT; Enzyme-Linked Immunospot Assay; Graft Rejection - immunology; Humans; induction; Kidney Transplantation - immunology; Lymphocyte Depletion - methods; Medical sciences; Prospective Studies; Receptors, Interleukin-2 - antagonists & inhibitors; Recombinant Fusion Proteins - therapeutic use; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; T-Lymphocytes - immunology; thymoglobulin; T‐cell; Suboptimal donor; T-cell; thymoglobulin; Transplantation; Homotransplantation; Immunity; Kidney; Allogeneic system; Surgery; Immunotherapy; T-Lymphocyte; Graft; Triggering; Antithymocyte globulin; Biological receptor; Human; Evaluation; Immune response; Induction; Donor immunity; Enzyme immunoassay; ELISPOT; Rejection; Treatment; Urinary system; Comparative study
• ISSN: 1600-6135; 1600-6143
• DOI: 10.1111/j.1600-6143.2011.03540.x

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.
Assessment of cellular alloreactivity in kidney transplant recipients receiving either a T cell depleting or a non‐T cell depleting antibody for induction therapy shows a differential effect on donor and nondonor alloimmune cellular responses. See editorial by Stock and Kirk on page 1349.