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 language | English (US) |
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Pages (from-to) | 1388-1396 |
Number of pages | 9 |
Journal | American Journal of Transplantation |
Volume | 11 |
Issue number | 7 |
DOIs | |
State | Published - Jul 2011 |
Externally published | Yes |
Keywords
- Donor immunity
- ELISPOT
- induction
- T-cell
- thymoglobulin
ASJC Scopus subject areas
- Transplantation
- Immunology and Allergy
- Pharmacology (medical)