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 allergic responses, have also been shown to actively participate to the build-up of protective host defense mechanisms. Recently, they have been shown to stimulate 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 mechanisms by which murine mast cells activate resting B and T lymphocytes, Methods: Mouse bone marrow-derived mast cells (BMMCs) or peritoneal mast cells were cocultured with resting splenocytes, Activation of B and T lymphocytes was assessed by measuring cell proliferation, blast formation, and cytokine release. Results: We report that addition of IL-4-treated BMMCs to normal spleen cells 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, We also demonstrate that mature mast cells in the peritoneal cavity are able to induce spleen cell activation and cytokine release. Addition of antileukocyte function-associated antigen 1 and anti-intercellular adhesion molecule 1 to the cocultures completely abrogates mast cell-induced blast formation and cytokine release. Experiments performed in vivo indicate that spleen cells from mice injected with BMMCs sustain their capacity of proliferation and cytokine production in vitro without any further stimulation. Conclusion: These observations suggest that mast cells may exert a helper effect on B and T lymphocytes, initiate T-H1-type immune responses, and may participate, through this mechanism, in the downregulation of allergic responses.