| First Author | Ruedl C | Year | 2000 |
| Journal | Eur J Immunol | Volume | 30 |
| Issue | 7 | Pages | 2056-64 |
| PubMed ID | 10940895 | Mgi Jnum | J:63646 |
| Mgi Id | MGI:1861331 | Doi | 10.1002/1521-4141(200007)30:7<2056::AID-IMMU2056>3.0.CO;2-S |
| Citation | Ruedl C, et al. (2000) The antigen dose determines T helper subset development by regulation of CD40 ligand. Eur J Immunol 30(7):2056-64 |
| abstractText | 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. |
