The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice

J Exp Med. 1992 Oct 1;176(4):1091-8. doi: 10.1084/jem.176.4.1091.

Abstract

To study the factors that determine whether CD4+ T cells produce interleukin 4 (IL-4) or interferon gamma (IFN-gamma) upon stimulation we used a system allowing naive T cells to be primed in vitro by specific antigen. Dense CD4+ T cells were purified from mice that expressed transgenes encoding a T cell receptor specific for pigeon cytochrome C peptide 88-104 in association with I-Ek. These T cells produced very limited amounts of IL-4 and IFN-gamma upon immediate challenge with 88-104 and antigen-presenting cells (APC). However, after an initial "priming" culture in which they were incubated for 4 d in the presence of 88-104, APC, and 1,000 U/ml IL-4, the T cells acquired the capacity to produce substantial amounts of IL-4 upon rechallenge but made very little IFN-gamma. Cells primed in the absence of IL-4 produced IFN-gamma upon rechallenge but virtually no IL-4. The inhibitory effect of IL-4 on IFN-gamma production did not appear to be mediated by the induction of IL-10 production since IL-10 addition to initial cultures did not suppress priming for IFN-gamma production, nor did anti-IL-10 block the inhibitory effect of IL-4. IFN-gamma itself did not increase priming for IFN-gamma production, nor did anti-IFN-gamma reduce such priming. IFN-gamma did, however, diminish priming for IL-4 production when limiting amounts of IL-4 (100 U/ml) were used in the initial culture. The dominant effect of IL-4 in determining the lymphokine-producing phenotype of primed cells was observed with dendritic cells (DC), activated B cells, and I-Ek-transfected fibroblasts as APC. However, the different APC did vary in their potency, with DC being superior to activated B cells, which were superior to transfected fibroblasts.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CD4 Antigens / immunology*
  • Cells, Cultured
  • Columbidae
  • Cytochrome c Group / chemical synthesis
  • Cytochrome c Group / immunology
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / pharmacology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Molecular Sequence Data
  • Oligopeptides / chemical synthesis
  • Oligopeptides / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / physiology*
  • Spleen / immunology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*

Substances

  • CD4 Antigens
  • Cytochrome c Group
  • Interleukin-2
  • Oligopeptides
  • Receptors, Antigen, T-Cell
  • Interleukin-4
  • Interferon-gamma