Nur77 Is Associated With Polyfunctional Properties in Virus-Specific Human CD8+ T Cells

  • Eur J Immunol. 2026 May;56(5):e70202. doi: 10.1002/eji.70202.
Fabiola Martel  1  2 ,  Daniel Rincón  2 ,  Caroline Passaes  3  4 ,  Leonardo Arévalo  5 ,  Marcela Torres  5 ,  Natalia Ramirez  5 ,  Carlos F Narváez  6 ,  Jessica F Toro  7 ,  Otto Sussmann  5 ,  Manuel A Franco  1  2 ,  José Mateus  8 ,  John Sidney  9 ,  Alessandro Sette  9 ,  Asier Sáez-Cirión  3  4 ,  Federico Perdomo-Celis  1  2
Affiliations
  • 1. Instituto de Genética Humana, Facultad de Medicina, Pontificia Universidad Javeriana, Bogotá, Colombia.
  • 2. CellRep Corporation, Dover, Delaware, USA.
  • 3. Institut Pasteur, Université Paris Cité, Viral Reservoirs and Immune Control Unit, Paris, France.
  • 4. Institut Pasteur, Université Paris Cité, HIV Inflammation and Persistence Unit, Paris, France.
  • 5. Infectoclinicos SAS, Bogota, Colombia.
  • 6. División de Inmunología, Programa de Medicina, Facultad de Ciencias de La Salud, Universidad Surcolombiana, Neiva, Huila, Colombia.
  • 7. Servicio de Pediatría, Clínica Medilaser, Neiva, Colombia.
  • 8. Vividion Therapeutics, San Diego, California, USA.
  • 9. Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, USA.
PMID: 42117214 DOI: 10.1002/eji.70202
Abstract

Human CD8+ T cells undergo significant metabolic and transcriptional shifts during activation and differentiation. The Orphan Nuclear Receptor Nur77 plays a role in modulating these processes and has been linked to T cell dysfunction. However, few studies have addressed its role in the memory potential and functionality of human CD8+ T cells. Here, we evaluated the expression of Nur77 in human CD8+ T cells, focusing on its relationship with their differentiation profile and functionality. Our findings indicate that Nur77 is associated with an early-differentiated, T cell factor 1+ (TCF-1+) memory-like phenotype in both total and virus-specific human CD8+ T cells across contexts of acute resolved or chronic viral Infection and vaccination. Nur77 expression was associated with cytokine polyfunctionality and increased proliferative capacity in long-lived antigen-responsive cells. Moreover, the modulation of Nur77 activity in vitro enhanced the functionality of chronic human immunodeficiency virus (HIV) and hepatitis B virus (HBV)-specific CD8+ T cells. These results suggest that Nur77 is associated with polyfunctional properties in virus-specific CD8+ T cell responses in humans. In addition, this study provides insights into novel strategies for enhancing CD8+ T cell functionality in settings of chronic antigen stimulation.

Keywords
CD8+ T cells; Nur77; human; memory; polyfunctionality; proliferation; stem‐like.
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