A study of the Nephrology and Renal Transplantation research group of the IDIBELL demonstrates that renal transplant patients who present regulatory T cells with high expression of FOXP3 factor demethylated, both in blood or directly into the transplanted organ, have a better functional outcome of the graft.
This is because these cells preserve their suppressor activity against allogeneic effector response (of organ rejection not recognized). The research results were published in the electronic edition of the American Journal of Transplantation.
The best-known function of lymphocytes or T cells in the context of the alloimmune response is the effector or inflammatory one, which is precisely what, causes rejection in organ transplantation. But there is a subtype of T cells, regulatory ones, whose function is precisely the regulation and modulation of effector immune response, are immunosuppressive and therefore very interesting in the field of transplantation.
The best known phenotype of these cells presented the transcription factor FOXP3 but in humans, Regulatory T cells don’t always have the regulatory function. Therefore IDIBELL researchers decided to characterize the epigenetic of these cells. The study of the chemical modifications present in the DNA of the transcription factor FOXP3.
The study was conducted in two groups of renal transplant patients: one with acute rejection and other with subclinical rejection (the functioning of the transplanted organ is good but a biopsy detects high levels of T cells that suggest a rejection). “In patients with acute rejection, T cells showed an epigenetic modification (methylation) in FOXP3” explained IDIBELL researcher and first author of the paper, Oriol Bestard, “while patients with subclinical rejection and good renal function did not have this change in FOXP3, they preserved the factor demethylated.”
Thus, this epigenetic change in FOXP3 serves as a biomarker of prognosis in kidney transplant. If it is demethylated these are cells with regulatory function of the immune response that will help us to control organ rejection.
The ultimate goal of research is to prevent that patients undergoing kidney transplantation have also to undergo an immunosuppressive therapy with adverse effects that this entails. “In Europe” Bestard explained, “have begun preliminary clinical studies with cell therapies to infuse regulatory T cells to transplant patients, with the results of this study, the therapy would be more accurate because we could infuse only regulatory T cells with FOXP3 factor demethylated, which are actually those that have immunoregulatory activity. ”
Article’s reference
Bestard O.*, Cuñetti L.*, Cruzado J.M.*, Lucia M.*, Valdez R.*, Olek S., Melilli E.*, Torras J.*, Mast R., Gomà M., Franquesa M.* and Grinyó J.M.*. Intragraft regulatory T cells in protocol biopsies retain Foxp3 Demethylation and are protective biomarkers for kidney graft outcome. American Journal of Transplantation. doi: 10.1111/j.1600-6143.2011.03633.x.
*IDIBELL researchers