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CD57(+) CD4 T Cells Underlie Belatacept-Resistant Allograft Rejection.
Espinosa, J; Herr, F; Tharp, G; Bosinger, S; Song, M; Farris, A B; George, R; Cheeseman, J; Stempora, L; Townsend, R; Durrbach, A; Kirk, A D.
Afiliación
  • Espinosa J; Department of Surgery, Emory University, Atlanta, GA.
  • Herr F; Department of Surgery, Duke University, Durham, NC.
  • Tharp G; INSERM UMR1014, Villejuif, France.
  • Bosinger S; Yerkes National Primate Research Center, Emory University, Atlanta, GA.
  • Song M; Yerkes National Primate Research Center, Emory University, Atlanta, GA.
  • Farris AB; Department of Surgery, Emory University, Atlanta, GA.
  • George R; Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA.
  • Cheeseman J; Department of Surgery, Emory University, Atlanta, GA.
  • Stempora L; Department of Surgery, Emory University, Atlanta, GA.
  • Townsend R; Department of Surgery, Duke University, Durham, NC.
  • Durrbach A; Department of Surgery, Emory University, Atlanta, GA.
  • Kirk AD; Department of Surgery, Duke University, Durham, NC.
Am J Transplant ; 16(4): 1102-12, 2016 Apr.
Article en En | MEDLINE | ID: mdl-26603381
Belatacept is a B7-specific fusion protein used to prevent allograft rejection by blocking T cell costimulation. Generally efficacious, it fails to prevent acute rejection in a sizable minority of patients. In experimental models, memory T cells mediate costimulation blockade-resistant rejection (CoBRR), but this remains undefined in humans. To explore relationships between individual patients' immune cell phenotypes and CoBRR, we studied patients receiving belatacept or conventional calcineurin inhibitor-based immunosuppression. We identified a population of CD57(+) PD1(-) CD4 T cells present prior to transplantation that correlated with CoBRR. Contrary to data recognizing CD57 as a marker of senescence on CD8 T cells, we discovered a nonsenescent, cytolytic phenotype associated with CD57 on CD4 T cells. Moreover, CD57(+) CD4 T cells expressed high levels of adhesion molecules implicated in experimental CoBRR, were CD28(-) , expressed a transcriptional phenotype broadly defining allograft rejection and were shown to be present in rejecting human kidney allografts. These data implicate CD57(+) CD4 T cells in clinical CoBRR. If prospectively validated, this characteristic could identify patients at higher risk for acute rejection on belatacept-based therapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Trasplante de Riñón / Antígenos CD57 / Abatacept / Rechazo de Injerto / Inmunosupresores Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Humans Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD4-Positivos / Trasplante de Riñón / Antígenos CD57 / Abatacept / Rechazo de Injerto / Inmunosupresores Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adult / Humans Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos