MOLECULAR MECHANISMS OF CHRONIC KIDNEY GRAFT INJURY

O. Thaunat¹, C. Deteix², B. Mcgregor³, V. Dubois⁴, E. Morelon^2
1Transplantation Rénale Et Immunologie Clinique, Hospices Civils de Lyon, Lyon/FRANCE, ²Dept Transplantation, Hopital Edouard Herriot, Lyon/FRANCE, ³Anatomopathologie, Hospices Civils de Lyon, Lyon/FRANCE, ⁴, EFS, Lyon/FRANCE

Body: Introduction: The progression of chronic rejection, one of the main cause of late allograft failure, is highly variable and difficult to forecast. Methods & Results: In order to evaluate theinfluence of intragraft inflammatory infiltrate on the course of chronic rejection, eleven human renal grafts, detransplanted for terminal failure, were analyzed. Samples were divided into two groupsaccording to their graft survival (> or ≤ 8 years). In both groups, the main cell population infiltrating the graft interstitia were T lymphocytes. The extent of thelymphocytic infiltration and the distribution of naive and memory, CD4+ and CD8+ T cells, were similar in both groups. While all types of T helper polarization profiles can lead to terminal chronicrejection, a correlation between shorter graft survival and the presence of Th17 cells which produce IL17 and IL21 was observed. In contrast, grafts infiltrated by regulatory T cells survivedsignificantly longer. The correlation between the expressions of activation-induced cytidine deaminase (the key enzyme of the germinal center reaction) and IL21 suggests that Th17 could exert theirdeleterious effect by promoting lymphoid neogenesis, i.e. the organization of inflammatory effectors into ectopic germinal centers in which a local humoral immune response is elicited. In accordancewith this hypothesis, immunofluorescence analysis evidenced a functional intragraft lymphoid tissue and an increased complement deposition in grafts infiltrated by Th17 cells. Conclusion: IntragraftTh17 infiltrate hastens clinical chronic rejection through the promotion of lymphoid neogenesis. Further studies will determine if Th17 infiltration can be used as a prognosis tool and if theTh17subset constitutes a therapeutic target for slowing down chronic rejection.

Disclosure: All authors have declared no conflicts of interest.