T-cell phenotype in protocol renal biopsy from transplant recipients treated with belatacept-mediated co-stimulatory blockade.

Philippe Grimbert, Vincent Audard, Carine Diet, Marie Matignon, Anne Plonquet, Hicham Mansour, Dominique Desvaux, Antoine Durrbach, José Laurent Cohen, Philippe Lang

Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2011;26(3):1087-93

PMID: 20667993

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Abstract

BACKGROUND

Belatacept is thought to disrupt the interaction between CD80/86 and CD28, thus preventing T-cell activation by blocking the co-stimulatory second signal. However, the consequences on the T-cell profile in human renal transplant cases have not been determined.

METHODS

In this study, we analysed intra-graft levels of the mRNAs for Treg (FOXP3), cytotoxic CD8 T cells (Granzyme B), Th1 (INFγ, Tbet), Th2 (GATA3) and Th17 (RORγt and IL-17) in protocol biopsies obtained 12 months after renal transplantation in recipients treated with Belatacept or calcineurin inhibitor (CNI).

RESULTS

Only the intra-graft abundance of FOXP3 mRNA was significantly lower (P < 0.001) in the Belatacept group than the CNI group. Conclusions. These results are in agreement with in vitro data suggesting that CD28 is a major co-stimulatory signal of both Tregs development and peripheral homeostasis but contrast with clinical trials showing a better 1-year graft function and a lower incidence of chronic allograft nephropathy in patients receiving Belatacept than patients treated with CNI. They suggest that immune benefits induced by Belatacept are not mediated by Treg expansion and that FOXP3 is not by itself a prognostic marker of long-term graft function in a non-inflammatory context. These results have to be, however, considered as preliminary since the size of our study population is limited.

Address: Department of Nephrology and Transplantation, Institut Mondor de Recherche Biomédicale INSERM U955, CHU Henri Mondor and Université Paris XII, Association pour l’Utilisation du Rein Artificiel, Créteil, France. [email protected]

DOI: 10.1093/ndt/gfq453

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MeSH Terms: Abatacept, B7-1 Antigen, B7-2 Antigen, Biopsy, CD28 Antigens, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Female, Flow Cytometry, Forkhead Transcription Factors, Graft Rejection, Humans, Immunoconjugates, Immunoenzyme Techniques, Immunosuppressive Agents, Interleukin-17, Kidney Diseases, Kidney Transplantation, Lymphocyte Activation, Male, Middle Aged, Phenotype, Prognosis, RNA, Messenger, Reverse Transcriptase Polymerase Chain Reaction, Risk Factors, Survival Rate, T-Lymphocytes, Regulatory, Th1 Cells, Th2 Cells, Transplantation Tolerance