Trichosanthin-stimulated dendritic cells induce a type 2 helper T lymphocyte response through the OX40 ligand.
Parole chiave
Astratto
BACKGROUND
Trichosanthin (TCS) induces a type 2 helper T lymphocyte (T(H)2) immune response that leads to the production of TCS-specific immunoglobulin (Ig) E and a subsequent allergic reaction in vivo. However, events immediately following treatment with TCS are poorly understood.
OBJECTIVE
We aimed to investigate whether dendritic cells (DCs) are the initial mediators of T(H)2 cell polarization induced by TCS and to investigate potential causative mechanisms
METHODS
DCs were cultured from purified human peripheral monocytes in the presence of granulocyte-macrophage colony-stimulating factor and interleukin (IL) 4. Flow cytometry was used to analyze cell surface antigen, intracellular cytokines, DC endocytic capacity, and apoptosis. The transcriptional profile for 120 genes in DCs was detected using oligonucleotide microarray analysis.
RESULTS
TCS exerted a cytotoxic effect on DCs in a concentration-dependent manner. Although TCS alone did not induce full maturation of DC, it did so in the presence of tumor necrosis factor alpha and IL-1beta in vitro. TCS-stimulated DCs induced a decreased ratio of T(H)1/T(H)2 cells derived from naïve T cells and showed selective expression of OX40 ligand (OX40L) at both mRNA and protein levels. This induction was partially blocked by anti-OX40L antibody.
CONCLUSIONS
Our results imply that TCS-stimulated DCs polarize the development of T(H)2 cells partially by means of the OX40L signal. Modulation of these DC will favor the alleviation of TCS-induced allergy.
