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Super-killer CTLs are generated by single gene deletion of Bach2.
Barton, Philippa R; Davenport, Alexander J; Hukelmann, Jens; Cantrell, Doreen A; Stinchcombe, Jane C; Richard, Arianne C; Griffiths, Gillian M.
Afiliação
  • Barton PR; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
  • Davenport AJ; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
  • Hukelmann J; Cell Signalling and Immunology Division, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
  • Cantrell DA; Cell Signalling and Immunology Division, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK.
  • Stinchcombe JC; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
  • Richard AC; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0XY, UK.
  • Griffiths GM; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0RE, UK.
Eur J Immunol ; 52(11): 1776-1788, 2022 11.
Article em En | MEDLINE | ID: mdl-36086884
Bach2 codes for a transcriptional regulator exerting major influences on T cell-mediated immune regulation. Effector CTLs derived from in vitro activation of murine CD8+ T cells showed increased proliferative and cytolytic capacity in the absence of BACH2. Before activation, BACH2-deficient splenic CD8+ T cells had a higher abundance of memory and reduced abundance of naïve cells compared to wild-type. CTLs derived from central memory T cells were more potently cytotoxic than those derived from naïve T cells, but even within separated subsets, BACH2-deficiency conferred a cytotoxic advantage. Immunofluorescence and electron microscopy revealed larger granules in BACH2-deficient compared to wild-type CTLs, and proteomic analysis showed an increase in granule content, including perforin and granzymes. Thus, the enhanced cytotoxicity observed in effector CTLs lacking BACH2 arises not only from differences in their initial differentiation state but also inherent production of enlarged cytolytic granules. These results demonstrate how a single gene deletion can produce a CTL super-killer.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD8-Positivos / Citotoxicidade Imunológica Limite: Animals Idioma: En Revista: Eur J Immunol Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T CD8-Positivos / Citotoxicidade Imunológica Limite: Animals Idioma: En Revista: Eur J Immunol Ano de publicação: 2022 Tipo de documento: Article