Allergic inflammation and Mast cells

The elicitation of IgE-mediated allergic inflammation, mast cells has been implicated in a range of other non-allergic inflammatory processes. Observations such as the close physical proximity between mast cells and T cells in inflamed tissues and the capability of the former to release a wide range of immunomodulatory mediators and to express surface molecules important in costimulation in both adaptive and innate immunity, have led investigators to propose a functional bi-directional relationship between these two cell populations. Indeed, morphologic studies have documented an increase in the local density of mast cells and their activation during T cell-mediated inflammatory processes, as observed in cutaneous delayed-type hypersensitivity, graft-versus-host reactions, sarcoidosis, Crohn’s disease, rheumatoid arthritis, and fibrosis. Both in vitro and in vivo studies have demonstrated that mast cells or their products are pivotal in mediating leukocyte recruitment into inflammatory sites, are capable of presenting antigens to T cells, interact directly with and affect the function of cells of the adaptive immune system, and mediate tissue remodeling. For instance, by using W/W^v mice reconstituted with mast cells obtained from TNF^−/− mice, it could be shown in vivo that TNF-α and MIP-2 (the functional murine analog of human IL-8) were essential for appropriate neutrophil recruitment during T cell-induced cutaneous delayed hypersensitivity reactions. Both cytokines were dependent on the presence of mast cells. The combination of these two mediators is crucial for cell recruitment because TNF-α and MIP-2 provide two qualitatively different but synergistic signals. The induction of MIP-2 and TNF-α were strictly dependent on the presence of mast cells and local activation of memory T cells, indicating that the infiltrating T cells deliver signals that induced both TNF-α and MIP-2 production by mast cells. However, the way by which T cells activate mast cells in T cell-mediated immune responses have not yet been fully elucidated

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Alex John
Editorial Assistant
Immunotherapy Open Access