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Specific CD4+ T cell phenotypes associate with bacterial control in people who 'resist' infection with Mycobacterium tuberculosis.
Sun, Meng; Phan, Jolie M; Kieswetter, Nathan S; Huang, Huang; Yu, Krystle K Q; Smith, Malisa T; Liu, Yiran E; Wang, Chuanqi; Gupta, Sanjana; Obermoser, Gerlinde; Maecker, Holden Terry; Krishnan, Akshaya; Suresh, Sundari; Gupta, Neha; Rieck, Mary; Acs, Peter; Ghanizada, Mustafa; Chiou, Shin-Heng; Khatri, Purvesh; Boom, W Henry; Hawn, Thomas R; Stein, Catherine M; Mayanja-Kizza, Harriet; Davis, Mark M; Seshadri, Chetan.
Afiliação
  • Sun M; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Phan JM; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
  • Kieswetter NS; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
  • Huang H; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Yu KKQ; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
  • Smith MT; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
  • Liu YE; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Wang C; Department of Epidemiology and Population Health, School of Medicine, Stanford University, Stanford, CA, USA.
  • Gupta S; Department of Immunology and Microbiology, University of Colorado, Anschutz Medicine Campus, Aurora, CO, USA.
  • Obermoser G; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Maecker HT; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Krishnan A; Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Suresh S; Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Gupta N; Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Rieck M; Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Acs P; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Ghanizada M; Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Chiou SH; Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Khatri P; Human Immune Monitoring Center, Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Boom WH; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Hawn TR; Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Stein CM; Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Department of Medicine, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.
  • Mayanja-Kizza H; Institute for Immunity, Transplantation and Infection, School of Medicine, Stanford University, Stanford, CA, USA.
  • Davis MM; Center for Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, CA, USA.
  • Seshadri C; Department of Biomedical Data Sciences, School of Medicine, Stanford University, Stanford, CA, USA.
Nat Immunol ; 2024 Jul 12.
Article em En | MEDLINE | ID: mdl-38997431
ABSTRACT
A subset of individuals exposed to Mycobacterium tuberculosis (Mtb) that we refer to as 'resisters' (RSTR) show evidence of IFN-γ- T cell responses to Mtb-specific antigens despite serially negative results on clinical testing. Here we found that Mtb-specific T cells in RSTR were clonally expanded, confirming the priming of adaptive immune responses following Mtb exposure. RSTR CD4+ T cells showed enrichment of TH17 and regulatory T cell-like functional programs compared to Mtb-specific T cells from individuals with latent Mtb infection. Using public datasets, we showed that these TH17 cell-like functional programs were associated with lack of progression to active tuberculosis among South African adolescents with latent Mtb infection and with bacterial control in nonhuman primates. Our findings suggested that RSTR may successfully control Mtb following exposure and immune priming and established a set of T cell biomarkers to facilitate further study of this clinical phenotype.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos