The antigen dose determines T helper subset development by regulation of CD40 ligand

Eur J Immunol. 2000 Jul;30(7):2056-64. doi: 10.1002/1521-4141(200007)30:7<2056::AID-IMMU2056>3.0.CO;2-S.


Although the amount of antigen and the strength of T cell stimulation have been suggested to regulate Th1 vs. Th2 polarization, it remains unclear how the antigen dose and the strength of signal is detected by the T cell and translated into differential cytokine production. Using co-cultures of dendritic cells (DC) and ovalbumin (OVA)-specific CD4+ T cells obtained from RAG-2)(-/-) DO11.10 mice, we show here that high-dose antigen induced Th1 development by up-regulation of CD40 ligand (CD40L), whereas low-dose antigen stimulation failed to induce CD40L and promoted Th2 development. CD40-CD40L interaction was essential for IL-12 production by DC. In the absence, de novo IL-4 production by T cells and autocrine Th2 development was induced. Furthermore, our results demonstrate that LFA-1/ ICAM interaction promotes Th1 differentiation by lowering the antigen dose required for CD40L up-regulation. Thus, we propose that (1) peptide-MHC density and (2) accessory molecules such as LFA-1 determine T helper polarization by regulation of CD40L.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD40 Antigens / immunology
  • CD40 Ligand
  • Cell Adhesion Molecules / immunology
  • Cells, Cultured
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Leukopoiesis
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mice, Transgenic
  • Ovalbumin / immunology*
  • Ovalbumin / pharmacology
  • Peptide Fragments / immunology*
  • Peptide Fragments / pharmacology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology
  • Th1 Cells / cytology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / cytology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*


  • CD40 Antigens
  • Cell Adhesion Molecules
  • Histocompatibility Antigens Class II
  • Lymphocyte Function-Associated Antigen-1
  • Membrane Glycoproteins
  • OVA 323-339
  • Peptide Fragments
  • CD40 Ligand
  • Ovalbumin