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Functional impairment of HIV-specific CD8+ T cells precedes aborted spontaneous control of viremia.
Collins, David R; Urbach, Jonathan M; Racenet, Zachary J; Arshad, Umar; Power, Karen A; Newman, Ruchi M; Mylvaganam, Geetha H; Ly, Ngoc L; Lian, Xiaodong; Rull, Anna; Rassadkina, Yelizaveta; Yanez, Adrienne G; Peluso, Michael J; Deeks, Steven G; Vidal, Francesc; Lichterfeld, Mathias; Yu, Xu G; Gaiha, Gaurav D; Allen, Todd M; Walker, Bruce D.
  • Collins DR; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • Urbach JM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Racenet ZJ; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Arshad U; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Power KA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Newman RM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Mylvaganam GH; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • Ly NL; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Lian X; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
  • Rull A; Joan XXIII University Hospital, Pere Virgili Institute (IISPV), Rovira i Virgili University, Tarragona, Spain.
  • Rassadkina Y; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
  • Yanez AG; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA.
  • Peluso MJ; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, CA, USA.
  • Deeks SG; Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, CA, USA.
  • Vidal F; Joan XXIII University Hospital, Pere Virgili Institute (IISPV), Rovira i Virgili University, Tarragona, Spain.
  • Lichterfeld M; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
  • Yu XG; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.
  • Gaiha GD; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.
  • Allen TM; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Walker BD; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Institute for Medical Engineering and Sciences and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: bwalker@mgh.harvard.edu.
Immunity ; 54(10): 2372-2384.e7, 2021 10 12.
Article en En | MEDLINE | ID: mdl-34496223
ABSTRACT
Spontaneous control of HIV infection has been repeatedly linked to antiviral CD8+ T cells but is not always permanent. To address mechanisms of durable and aborted control of viremia, we evaluated immunologic and virologic parameters longitudinally among 34 HIV-infected subjects with differential outcomes. Despite sustained recognition of autologous virus, HIV-specific proliferative and cytolytic T cell effector functions became selectively and intrinsically impaired prior to aborted control. Longitudinal transcriptomic profiling of functionally impaired HIV-specific CD8+ T cells revealed altered expression of genes related to activation, cytokine-mediated signaling, and cell cycle regulation, including increased expression of the antiproliferative transcription factor KLF2 but not of genes associated with canonical exhaustion. Lymphoid HIV-specific CD8+ T cells also exhibited poor functionality during aborted control relative to durable control. Our results identify selective functional impairment of HIV-specific CD8+ T cells as prognostic of impending aborted HIV control, with implications for clinical monitoring and immunotherapeutic strategies.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Viremia / Infecciones por VIH / Linfocitos T CD8-positivos Tipo de estudio: Prognostic_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Viremia / Infecciones por VIH / Linfocitos T CD8-positivos Tipo de estudio: Prognostic_studies Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Año: 2021 Tipo del documento: Article