Investigation of the role of cholera toxin in assisting the initiation of the antigen-specific Th2 response.

Skewed Th2 polarization and tissue mastocytosis are the main features of allergy; but how the antigen-specific Th2 polarization initiated remains unclear. The present study shows that cholera toxin (CT) activates mouse bone marrow mast cells (BMMC) to release interleukin (IL)-4. The activation process involved in Toll-like receptor 4, nucleotide oligomerisation domain 1, activate signal transducer and activator of transcription 6 (STAT6), and IL-4. Activated mast cell-derived IL-4 in synergy with co-existing antigen information provided by dendritic cells drives naive CD4+ T cells to differentiate into antigen-specific Th2 cells. The finding demonstrates that concurrent exposure to microbial products, such as CT, and antigen-loaded dendritic cells plays a critical role in the initiation of antigen-specific Th2 response in the body; this notion is supported by the concurrent adoptive transfer with CT-pulsed BMMCs and antigen-loaded BMDCs that induced antigen-specific Th2 response and hypersensitivity reaction in the intestine.