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Low-dose interleukin-2 promotes immune regulation in face transplantation: A pilot study.
Murakami, Naoka; Borges, Thiago J; Win, Thet Su; Abarzua, Phammela; Tasigiorgos, Sotirios; Kollar, Branislav; Barrera, Victor; Ho Sui, Shannan; Teague, Jessica E; Bueno, Ericka; Clark, Rachael A; Lian, Christine G; Murphy, George F; Pomahac, Bohdan; Riella, Leonardo V.
Afiliación
  • Murakami N; Transplant Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Borges TJ; Transplant Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Win TS; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Abarzua P; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Tasigiorgos S; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Kollar B; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Medical Faculty of the University of Freiburg, Freiburg, Germany.
  • Barrera V; Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Maryland, USA.
  • Ho Sui S; Bioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Maryland, USA.
  • Teague JE; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Bueno E; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Clark RA; Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Lian CG; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Murphy GF; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA.
  • Pomahac B; Division of Plastic Surgery, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Department of Surgery, Division of Plastic and Reconstructive Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, Connecticut, USA. Electronic address: b
  • Riella LV; Transplant Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, Maryland, USA; Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School, Boston, Maryland, USA. Electronic address: lriella@mgh.harvard.edu.
Am J Transplant ; 23(4): 549-558, 2023 04.
Article en En | MEDLINE | ID: mdl-36740193
Face transplantation is a life-changing procedure for patients with severe composite facial defects. However, it is hampered by high acute rejection rates due to the immunogenicity of skin allograft and toxicity linked to high doses of immunosuppression. To reduce immunosuppression-associated complications, we, for the first time in face transplant recipients, used low-dose interleukin 2 (IL-2) therapy to expand regulatory T cells (Tregs) in vivo and to enhance immune modulation, under close immunological monitoring of peripheral blood and skin allograft. Low-dose IL-2 achieved a sustained expansion (∼4-fold to 5-fold) of circulating Tregs and a reduction (∼3.5-fold) of B cells. Post-IL-2 Tregs exhibited greater suppressive function, characterized by higher expression of TIM-3 and LAG3co-inhibitory molecules. In the skin allograft, Tregs increased after low-dose IL-2 therapy. IL-2 induced a distinct molecular signature in the allograft with reduced cytotoxicity-associated genes (granzyme B and perforin). Two complications were observed during the trial: one rejection event and an episode of autoimmune hemolytic anemia. In summary, this initial experience demonstrated that low-dose IL-2 therapy was not only able to promote immune regulation in face transplant recipients but also highlighted challenges related to its narrow therapeutic window. More specific targeted Treg expansion strategies are needed to translate this approach to the clinic.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-2 / Trasplante Facial Límite: Humans Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Interleucina-2 / Trasplante Facial Límite: Humans Idioma: En Revista: Am J Transplant Asunto de la revista: TRANSPLANTE Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos