IMMUNE REGULATION AND TOLERANCE II

T. Kandeva¹, S. Liu², J. Tchervenkov^2
1Surgery, McGill University Health Center, Montreal/QC/CANADA, ²Surgery, McGill University Health Centre, Montreal/QC/CANADA

Body: Introduction: Interleukin 17 (IL-17) and the more-recently characterized CD4⁺T_H17 lymphocytes are shown to have a central role in pro-inflammatory processes. These cells have been primarily studied in autoimmune disease and there is evidence of their implication in animal models of organ rejection. However, the role of IL-17 and T_H17 lymphocytes in the context of human kidney transplantation is not yet fully characterized. Highly-sensitized (HS) patients waiting for a kidney transplant have a heightened immunity as shown by the presence of high levels of anti-donor antibodies and have a greater risk for both T-cell and antibody-mediated rejection. In animal models of autoimmune disease, T_H17-lymphocytes were shown to be involved in B-lymphocyte activation and antibody production. We therefore investigated if HS renal transplant patients (PRA >60%) have increased number of circulating peripheral T_H17 lymphocytes and a greater IL-17 cytokine production in comparison to healthy subjects. Methods: HS renal transplants on the waiting list (n=14: PRAs > 60%; mean HLA I: 87.25%, HLA II: 82.3%) were compared to healthy subject controls (n=14). Immune responsiveness was quantified by the ATP concentration in CD4⁺T-cells using the Cylex® Immune cell-function assay. The supernatant from this assay was then collected and IL-17, IFN-γ and IL-6 were measured by ELISA. The presence of CD4⁺T_H17 cells was quantified by flow cytometric analysis of intracellular IL-17 after PMA- Ionomycin stimulation. IL-17 receptor (IL-17R) on ex-vivo peripheral mononuclear cells was measured using FACS analysis. Results: Cylex® assays showed a heightened immune responsiveness of total CD4⁺T cells in HS patients as compared to healthy adults controls (590 ng/ml ATP vs. 442 ng/ml ATP, P<0.05). IL-17 production by stimulated CD4⁺T cells in HS patients was increased (P<0.01) (figure, left) whereas IL-6 and IFN- γ was not (P=0.55 and P=0.10 respectively). Peripheral T_H17 lymphocytes, as measured by intracellular IL-17 production of stimulated lymphocytes (figure, right) was higher in HS patients (P<0.05). An increase of IL-17R expression was seen on peripheral lymphocytes in HS patients (P=0.001) whereas IL-6R expression was similar in both groups. The increase in IL-17R was accounted for by neither the CD3⁺ nor the CD19⁺ population. Conclusion: This data suggests that, in HS renal transplant patients, there is an elevated presence of peripheral T_H17 cells and an increased expression of IL-17R on non-B and -T lymphocytes. This may be important in the overall heightened immunity of HS patients and can thus be of interest in the modulation of immune responses in this patient population.

Disclosure: All authors have declared no conflicts of interest.