Characterization of immune tolerance by donor bone-marrow transplantation in kidney transplanted patients

Abstract

Kidney transplantation (KT) is successfully carried out with immunosuppressive treatment of recipients. However, recipients receiving immunosuppressants are at great risk of viral infections or cancer due to life-long duration of the treatment. Therefore, studies have been performed for alternative protocols in attempt to overcome such complications, including infusion of regulatory T cells (Tregs) and administration of blocking antibodies against co-stimulatory molecules. Among those is to perform bone marrow transplantation (BMT) simultaneously with KT (BMTKT) to induce mixed chimerism in the recipient and establish immune tolerance to the grafted organ. In the current research, we conducted BMTKT by recruiting six patients who are living donor KT recipients and each have a one-haplotype match donor. In these patients, we analyzed the recipients’ peripheral blood mononuclear cells collected at various time-points throughout the transplantation period to investigate the dynamics and phenotypes of various immune cell populations including memory CD4^{+} and CD8^{+} T cells, and Tregs and subsets within the population. As of result, we found the ratio of CD45RA^{-}Foxp3^{bright} Tregs (effector Tregs with suppressive function) to CD45RA^{-}Foxp3^{dim} Tregs (non-suppressive, pro-inflammatory cytokine producing cells) as a unique biomarker of immune tolerance. In addition, there was a difference in the frequency of Tregs in mixed lymphocyte reaction (MLR) assay between patients experienced rejection episodes and those who have not. Collectively, our study reports that Tregs play a role in inducing donor-related immune tolerance in BMTKT patients.