Mast cell activation and vascular alterations in immediate hypersensitivity-like reactions induced by a T...

Previous studies have shown that T cell-dependent activation of mast cells to release serotonin is required for the elicitation of delayed-type hypersensitivity in mice. We have recently described an antigen-binding T cell factor that is a suitable candidate for participation in the mechanism by which T cells activate mast cells in delayed-type hypersensitivity. The T cell factor transfers the ability to elicit an antigen-specific immediate hypersensitivity-like ear-swelling reaction following local challenge with antigen. In the current study, alterations in the morphology of local tissue mast cells and vessels were studied by light and electron microscopy at the time of optimal swelling and increase in vascular permeability. Factor-induced reactions showed mild changes in metachromatic staining of mast cell granules compared with more profound changes that were found in reactions of antigen-challenged mice that were sensitized by intravenous injection with IgE antibody. Subtle changes in the ultrastructure of mast cells in reactions induced by the T cell factor included surface activation to form filopodial extensions, resulting in a significant increase in the surface density by stereologic analysis. The cytoplasm of these mast cells also showed signs of synthetic and metabolic activity with formation of vesicles and an increased prominence of the Golgi apparatus and mitochondria. Local vessels at sites of reactions due to the T cell factor or IgE showed intravascular accumulation of polymorphonuclear leukocytes, gaps at sites of endothelial cell junctions, and occasional emigration of the leukocytes into the perivascular area. This indicates that a vasoactive factor, such as serotonin, and chemotactic factors were released in both instances. However, in recipients of the T cell factor, this was accomplished with only moderate signs of overt mast cell degranulation and loss of granule density. Instead, there was formation of vesicles at the outer margin of the granules, in the perigranular membrane, and in the cytoplasm, accompanied by the surface activation. In contrast, mast cells from reactions in IgE-sensitized animals appeared to degranulate by a process of sequential compound exocytosis with no vesicle formation or cytoplasmic findings of increased synthetic or metabolic activity. The granules of these cells showed a great loss of density and many appeared swollen, resulting in overall swelling and increase in area of the cell.(ABSTRACT TRUNCATED AT 400 WORDS)