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

Journal article

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.

Authors: Ruedl, C; Bachmann, M; Kopf, M

• Publication status: Published
• Journal: European journal of immunology
• Volume: 30
• Issue: 7
• Pages: 2056-2064
• Publication date: 2000-07-01
• DOI: 10.1002/1521-4141(200007)30:7<2056::aid-immu2056>3.0.co;2-s
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Histocompatibility Antigens Class II; Mice, Transgenic; Cell Adhesion Molecules; Mice; Male; Membrane Glycoproteins; Ovalbumin; Leukopoiesis; Th1 Cells; Th2 Cells; Peptide Fragments; CD40 Ligand; Cells, Cultured; Female; Mice, Inbred BALB C; Lymphocyte Function-Associated Antigen-1; Animals; Antigens, CD40; Mice, Knockout; T-Lymphocyte Subsets