2. Academic Validation
  3. Nur77 Is Associated With Polyfunctional Properties in Virus-Specific Human CD8+ T Cells

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

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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