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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.

Original publication

DOI

10.1002/1521-4141(200007)30:7<2056::AID-IMMU2056>3.0.CO;2-S

Type

Journal article

Journal

Eur J Immunol

Publication Date

07/2000

Volume

30

Pages

2056 - 2064

Keywords

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