title: T-cell phenotype in protocol renal biopsy from transplant recipients treated with belatacept-mediated co-stimulatory blockade.
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.
authors.affiliation: 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. philippe.grimbert@hmn.aphp.fr
authors.forename: Philippe
authors.initials: P
authors.lastname: Grimbert
authors.forename: Vincent
authors.initials: V
authors.lastname: Audard
authors.forename: Carine
authors.initials: C
authors.lastname: Diet
authors.forename: Marie
authors.initials: M
authors.lastname: Matignon
authors.forename: Anne
authors.initials: A
authors.lastname: Plonquet
authors.forename: Hicham
authors.initials: H
authors.lastname: Mansour
authors.forename: Dominique
authors.initials: D
authors.lastname: Desvaux
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: José Laurent
authors.initials: JL
authors.lastname: Cohen
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
mesh_terms: D000069594:Abatacept; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D001706:Biopsy; D018106:CD28 Antigens / Q000276:immunology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020381:Interleukin-17 / Q000378:metabolism; D007674:Kidney Diseases / Q000276:immunology / Q000601:surgery; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D023001:Transplantation Tolerance / Q000187:drug effects* / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D012333:RNA, Messenger; D000069594:Abatacept