title: Trichosanthin-stimulated dendritic cells induce a type 2 helper T lymphocyte response through the OX40 ligand.
abstract: 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.
authors: Institute of Medical Biotechnology, Soochow University, Suzhou, China.
authors: R
authors: R
authors: Yan
authors: W
authors: W
authors: Zhong
authors: Y
authors: Y
authors: Zhu
authors: X
authors: X
authors: Zhang
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D002469:Cell Separation; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D053278:OX40 Ligand / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D015978:Trichosanthin / Q000276:immunology* / Q000494:pharmacology
chemical_list: D053278:OX40 Ligand; D015978:Trichosanthin