In vitro and in vivo immunostimulatory potential of bone marrow-derived mast cells on B- and T-lymphocyte activation

Background: Mast cells, which play a unique role in inflammatory and allerg ic responses, have also been shown to actively participate to the build-up of protective host defense mechanisms. Recently, they have been shown to st imulate resting B cells and to form heterotypic aggregates with activated T cells, resulting in mast cell degranulation. Objectives: Our aim is to investigate the cytokine requirements and the mec hanisms by which murine mast cells activate resting B and T lymphocytes, Methods: Mouse bone marrow-derived mast cells (BMMCs) or peritoneal mast ce lls were cocultured with resting splenocytes, Activation of B and T lymphoc ytes was assessed by measuring cell proliferation, blast formation, and cyt okine release. Results: We report that addition of IL-4-treated BMMCs to normal spleen cel ls resulted within 48 hours in a B- and T-cell activation with substantial amounts of the T-H1 cytokines IFN-gamma and IL-12 and no detectable IL-4, W e also demonstrate that mature mast cells in the peritoneal cavity are able to induce spleen cell activation and cytokine release. Addition of antileu kocyte function-associated antigen 1 and anti-intercellular adhesion molecu le 1 to the cocultures completely abrogates mast cell-induced blast formati on and cytokine release. Experiments performed in vivo indicate that spleen cells from mice injected with BMMCs sustain their capacity of proliferatio n and cytokine production in vitro without any further stimulation. Conclusion: These observations suggest that mast cells may exert a helper e ffect on B and T lymphocytes, initiate T-H1-type immune responses, and may participate, through this mechanism, in the downregulation of allergic resp onses.