Precursor central memory versus effector cell fate and naïve CD4+ T cell heterogeneity. Academic Article uri icon

Overview

abstract

  • Upon antigenic stimulation, naïve CD4+ T cells can give rise to phenotypically distinct effector T helper cells and long-lived memory T cells. We computationally reconstructed the in vivo trajectory of CD4+ T cell differentiation during a type I inflammatory immune response and identified two distinct differentiation paths for effector and precursor central memory T cells arising directly from naïve CD4+ T cells. Unexpectedly, our studies revealed heterogeneity among naïve CD4+ T cells, which are typically considered homogeneous save for their diverse T cell receptor usage. Specifically, a previously unappreciated population of naïve CD4+ T cells sensing environmental type I IFN exhibited distinct activation thresholds, suggesting that naïve CD4+ T cell differentiation potential may be influenced by environmental cues. This population was expanded in human viral infection and type I IFN response-lined autoimmunity. Understanding the relevance of naïve T cell heterogeneity to beneficial and maladaptive T cell responses may have therapeutic implications for adoptive T cell therapies in cancer immunotherapy and vaccination.

publication date

  • September 25, 2024

Research

keywords

  • CD4-Positive T-Lymphocytes
  • Cell Differentiation
  • Immunologic Memory
  • Memory T Cells

Identity

Digital Object Identifier (DOI)

  • 10.1084/jem.20231193

PubMed ID

  • 39321257

Additional Document Info

volume

  • 221

issue

  • 10