The antigen dose determines T helper subset development by regulation of CD40 ligand.
Eur J Immunol
; 30(7): 2056-64, 2000 Jul.
Article
in En
| MEDLINE
| ID: mdl-10940895
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptide Fragments
/
Membrane Glycoproteins
/
Ovalbumin
/
Th2 Cells
/
Th1 Cells
Limits:
Animals
Language:
En
Journal:
Eur J Immunol
Year:
2000
Document type:
Article
Affiliation country:
Suiza
Publication country:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY