IL-2 secretion by CD4+ T cells in vivo is rapid, transient, and influenced by TCR-specific competition

J Immunol. 2004 May 15;172(10):6136-43. doi: 10.4049/jimmunol.172.10.6136.

Abstract

The secretion of IL-2 is a critical and early landmark in the activation program of CD4(+) T cells in vitro, but the lack of sensitive assays has limited its application for studying T cell activation in vivo. Using a mouse cytokine capture assay we were able to detect the rapid secretion of IL-2 after an in vivo stimulus by 1-2 h in naive T cells and as early as 30 min in memory T cells. Maximal secretion was achieved within 1-2 h for memory cells or 6-8 h for naive T cells. Surprisingly IL-2 production terminated quickly in vivo and secretion was undetectable by 20-24 h in either cell type. We further demonstrated that this short duration of secretion can be influenced by cellular competition between Ag-specific CD4(+) T cells. The consequences of competition were mimicked by reducing the strength of the antigenic stimulus. These data argue that early competition between T cells influences both the eventual frequency of IL-2 producers in the population and also the duration of their secretion, potentially by altering the strength or duration of the stimulus available to each T cell.

Publication types

  • Comparative Study

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Bacterial / administration & dosage
  • Antigens, Bacterial / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cell Communication / genetics
  • Cell Communication / immunology*
  • Clone Cells
  • Dose-Response Relationship, Immunologic
  • Enterotoxins / administration & dosage
  • Enterotoxins / immunology
  • Epitopes, T-Lymphocyte / immunology*
  • Injections, Intraperitoneal
  • Interleukin-2 / biosynthesis
  • Interleukin-2 / metabolism*
  • Kinetics
  • Lymphocyte Activation
  • Lymphocyte Count
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred A
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*
  • Staphylococcus aureus / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / transplantation

Substances

  • Antigens, Bacterial
  • Enterotoxins
  • Epitopes, T-Lymphocyte
  • Interleukin-2
  • Receptors, Antigen, T-Cell
  • enterotoxin A, Staphylococcal