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Belatacept-Resistant Rejection Is Associated With CD28+ Memory CD8 T Cells.
Mathews, D V; Wakwe, W C; Kim, S C; Lowe, M C; Breeden, C; Roberts, M E; Farris, A B; Strobert, E A; Jenkins, J B; Larsen, C P; Ford, M L; Townsend, R; Adams, A B.
Afiliación
  • Mathews DV; Emory Transplant Center, Atlanta, GA.
  • Wakwe WC; Emory Transplant Center, Atlanta, GA.
  • Kim SC; Emory Transplant Center, Atlanta, GA.
  • Lowe MC; Emory Transplant Center, Atlanta, GA.
  • Breeden C; Emory Transplant Center, Atlanta, GA.
  • Roberts ME; Bristol-Myers Squibb, Princeton, NJ.
  • Farris AB; Emory Transplant Center, Atlanta, GA.
  • Strobert EA; Yerkes National Primate Center, Atlanta, GA.
  • Jenkins JB; Yerkes National Primate Center, Atlanta, GA.
  • Larsen CP; Emory Transplant Center, Atlanta, GA.
  • Ford ML; Yerkes National Primate Center, Atlanta, GA.
  • Townsend R; Emory Transplant Center, Atlanta, GA.
  • Adams AB; Bristol-Myers Squibb, Princeton, NJ.
Am J Transplant ; 17(9): 2285-2299, 2017 Sep.
Article en En | MEDLINE | ID: mdl-28502128
Recently, newer therapies have been designed to more specifically target rejection in an effort to improve efficacy and limit unwanted toxicity. Belatacept, a CD28-CD80/86 specific reagent, is associated with superior patient survival and graft function compared with traditional therapy, but its adoption as a mainstay immunosuppressive therapy has been tempered by increased rejection rates. It is essential that the underlying mechanisms associated with this rejection be elucidated before belatacept is more widely used. To that end, we designed a study in a nonhuman primate kidney transplant model where animals were treated with either a belatacept- or a tacrolimus-based immunosuppressive regimen. Interestingly, we found that elevated pretransplant frequencies of CD28+ CD8+ TEMRA cells are associated with rejection on belatacept but not tacrolimus treatment. Further analysis showed that the CD28+ CD8+ TEMRA cells rapidly lose CD28 expression after transplant in those animals that go on to reject with the allograft infiltrate being predominantly CD28- . These data suggest that CD28+ memory T cells may be resistant to belatacept, capable of further differentiation including loss of CD28 expression while maintaining effector function. The unique signaling requirements of CD28+ memory T cells provide opportunities for the development of targeted therapies, which may synergize with belatacept to prevent costimulation-independent rejection.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Resistencia a Medicamentos / Trasplante de Riñón / Antígenos CD28 / Linfocitos T CD8-positivos / Abatacept / Rechazo de Injerto / Memoria Inmunológica Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2017 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: Resistencia a Medicamentos / Trasplante de Riñón / Antígenos CD28 / Linfocitos T CD8-positivos / Abatacept / Rechazo de Injerto / Memoria Inmunológica Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Animals Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2017 Tipo del documento: Article Pais de publicación: Estados Unidos