A distinct priming phase regulates CD8 T cell immunity by orchestrating paracrine IL-2 signals

Science. 2025 Apr 11;388(6743):eadq1405. doi: 10.1126/science.adq1405. Epub 2025 Apr 11.

Abstract

T cell priming is characterized by an initial activation phase that involves stable interactions with dendritic cells (DCs). How activated T cells receive the paracrine signals required for their differentiation once they have disengaged from DCs and resumed their migration has been unclear. We identified a distinct priming phase that favors CD8 T cells expressing receptors with high affinity for antigen. CXCR3 expression by CD8 T cells was required for their hours-long reengagement with DCs in specific subfollicular niches in lymph nodes. CD4 T cells paused briefly at the sites of CD8 T cell and DC interactions and provided Interleukin-2 (IL-2) before moving to another DC. Our results highlight a previously unappreciated phase of cell-cell interactions during T cell priming and have direct implications for vaccinations and cellular immunotherapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes* / immunology
  • Cell Communication
  • Cell Movement
  • Dendritic Cells* / immunology
  • Interleukin-2* / immunology
  • Interleukin-2* / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C57BL
  • Paracrine Communication*
  • Receptors, CXCR3 / genetics
  • Receptors, CXCR3 / immunology
  • Receptors, CXCR3 / metabolism

Substances

  • Interleukin-2
  • Receptors, CXCR3
  • Cxcr3 protein, mouse