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RI-Dependent Mast Cell Degranulation Following Coculture with Activated T Cells: Dependency on ICAM-1- and Leukocyte Function-Associated Antigen (LFA)-1-Mediated Heterotypic Aggregation
*
Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Fujisawa Pharmaceutical Co., Ibaraki, Japan; and
Department of Medicine, Meir General Hospital, Kfar-Saba, and the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
Activated mast cells are known to reside in close
apposition to T cells in various inflammatory processes. In
this regard, we have reported that activated mast cells form
heterotypic aggregates with activated lymphocytes. To determine whether
this interaction would result in mast cell degranulation, we examined
the effect of EL-4, 2B4, or freshly isolated T cells, activated by PMA
or immobilized anti-CD3 mAb, on histamine release from murine bone
marrow-derived cultured mast cells (BMCMC). Coculturing BMCMC with
activated but not with resting T cells resulted in significant
histamine release. Also, Fc
RI cross-linking-induced degranulation
was augmented when BMCMC were cocultured with activated T cells.
Supernatants of activated T cells failed to exert the stimulatory
effect. Separation of the two cell populations with a porous membrane
prevented degranulation, indicating that BMCMC activation was adhesion
dependent. Indeed, the kinetics of histamine release paralleled the
kinetics of the formation of heterotypic aggregates, which peaked after
12 h of coculture. Introduction of anti-LFA-1 and
anti-intercellular adhesion molecule-1 mAb inhibited the
adhesion-induced mast cell degranulation. These data suggest a
heretofore unrecognized mast cell activation pathway induced by
LFA-1/intercellular adhesion molecule-1-mediated heterotypic
aggregation with activated T cells.
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