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Beta cell-specific CD8+ T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes.
Abdelsamed, Hossam A; Zebley, Caitlin C; Nguyen, Hai; Rutishauser, Rachel L; Fan, Yiping; Ghoneim, Hazem E; Crawford, Jeremy Chase; Alfei, Francesca; Alli, Shanta; Ribeiro, Susan Pereira; Castellaw, Ashley H; McGargill, Maureen A; Jin, Hongjian; Boi, Shannon K; Speake, Cate; Serti, Elisavet; Turka, Laurence A; Busch, Michael E; Stone, Mars; Deeks, Steven G; Sekaly, Rafick-Pierre; Zehn, Dietmar; James, Eddie A; Nepom, Gerald T; Youngblood, Ben.
Afiliación
  • Abdelsamed HA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Zebley CC; Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
  • Nguyen H; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Rutishauser RL; Graduate School of Biomedical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Fan Y; Translational Research Program, Benaroya Research Institute, Seattle, WA, USA.
  • Ghoneim HE; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Crawford JC; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Alfei F; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Alli S; Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, USA.
  • Ribeiro SP; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Castellaw AH; Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
  • McGargill MA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Jin H; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
  • Boi SK; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Speake C; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Serti E; Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Turka LA; Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Busch ME; Diabetes Research Program, Benaroya Research Institute, Seattle, WA, USA.
  • Stone M; Immune Tolerance Network, Bethesda, MD, USA.
  • Deeks SG; Immune Tolerance Network, Bethesda, MD, USA.
  • Sekaly RP; Center for Translational Sciences, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
  • Zehn D; Vitalant Research Institute, San Francisco, CA, USA.
  • James EA; Vitalant Research Institute, San Francisco, CA, USA.
  • Nepom GT; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Youngblood B; Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Nat Immunol ; 21(5): 578-587, 2020 05.
Article en En | MEDLINE | ID: mdl-32231298
The pool of beta cell-specific CD8+ T cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell 'multipotency index' and found that beta cell-specific CD8+ T cells retained a stem-like epigenetic multipotency score. Single-cell assay for transposase-accessible chromatin using sequencing confirmed the coexistence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8+ T cells. Assessment of beta cell-specific CD8+ T cell anatomical distribution and the establishment of stem-associated epigenetic programs revealed that self-reactive CD8+ T cells isolated from murine lymphoid tissue retained developmentally plastic phenotypic and epigenetic profiles relative to the same cells isolated from the pancreas. Collectively, these data provide new insight into the longevity of beta cell-specific CD8+ T cell responses and document the use of this methylation-based multipotency index for investigating human and mouse CD8+ T cell differentiation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T CD8-positivos / Células Madre Pluripotentes / Diabetes Mellitus Tipo 1 / Células Secretoras de Insulina Tipo de estudio: Risk_factors_studies Límite: Adolescent / Adult / Animals / Female / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos 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 CD8-positivos / Células Madre Pluripotentes / Diabetes Mellitus Tipo 1 / Células Secretoras de Insulina Tipo de estudio: Risk_factors_studies Límite: Adolescent / Adult / Animals / Female / Humans / Male Idioma: En Revista: Nat Immunol Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos