Cell-cell cooperation at the T helper cell/mast cell immunological synapse

Abstract

IntroductionMast cells are known to play a pivotal role in allergic hypersensitivity reaction and, more generally, in inflammation. 1,2 By virtue of their strategic and widespread location in tissues, namely at host-environment interface, and of their functional characteristics, mast cells behave as sentinels of the immune system. 3 Once activated, mast cells release several preformed and de novosynthesized mediators (including histamine, proteases, leukotrienes, prostaglandins, and various cytokines and chemokines), resulting in the recruitment and activation of other immune cells. 3 Several lines of evidence highlight an emerging role of mast cells in numerous steps of innate and adaptive immune responses, indicating that their contribution to immunity goes far beyond their well-known role in allergy. [3][4][5][6][7][8] Functional interplay between mast cells and T cells has been suggested by studies that document colocalization of activated mast cells and T cells in inflamed tissues 9,10 or involvement of mast cells in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. [11][12][13] Additional lines of evidence show that mast cells can contribute to the development of different T cell-associated responses by influencing the activation, the proliferation, the differentiation, and the recruitment of T cells. 7,14,15 Recent in vitro studies showed that IgE-activated mast cells can enhance T-cell proliferation by a mechanism involving tumor necrosis factor ␣ (TNF-␣) secretion, cell contact, and mast cell expression of OX40L. 6,7 In turn, it has been shown that activated T cells can induce in vitro histamine, TNF-␣, matrix metalloproteinase-9 secretion, and interleukin 4 (IL-4) mRNA expression in mast cell subsets. [16][17][18] Finally, mast cells have been reported to promote in vivo T-cell migration to inflammatory sites by secreting chemotactic factors, such as lymphotactin and IL-16 19 and to orient Th differentiation via the production of 21 Taken together these studies highlight the existence of functionally important mast cell/T-cell crosstalk and raise the question of whether mast cell/T-cell cognate interactions might occur in the course of immune responses.Immunological synapses (ISs) are the morphologic manifestation of the cognate interactions occurring between T cells and other cells of the immune system serving as antigen-presenting cells (APCs). These specialized areas of signal transduction, formed at the T cell/APC contact site, are characterized by large scale clustering and segregation of surface molecules and intracellular signaling components. [22][23][24] Among the different molecular rearrangements occurring at the IS, the polarization of T-cell Golgi apparatus toward the APCs for polarized secretion is a distinctive, rapid, and efficient T-cell response, occurring within minutes after T cell/APC encounter both in resting and activated CD4 ϩ and CD8 ϩ T cells. [25][26][27] It is, therefore, considered, together with T-cell receptor (TCR) enrichment into the IS, a morphol...

Mast cells in early rheumatoid arthritis associate with disease severity and support B cell autoantibody production

“…Importantly, we demonstrate that MCs induce ACPA production by B cells, also in a contact-dependent manner, although the relevance of CD40L expression by MCs in the induction of ACPA remains to be confirmed. Furthermore, we provide the first evidence of an active interaction between human MCs and B cells, as previously shown for MC–T cells50 and MC–Dendritic Cells 51 . In vivo , we used AIA to assess the time course and magnitude of synovial MC infiltration, and IL27 ra -deficient mice as a model of exacerbated synovitis accompanied by ELS formation,33 thus resembling RA patients with a lymphoid pathotype.…”

Mast cells aggravate sepsis by inhibiting peritoneal macrophage phagocytosis

“…This secretion was not accompanied by the release of granule content (data not shown), an indication that, in these cells, IL-4 is not stored in histamine-containing granules, thus revealing a degree of selectivity for bacteria-induced IL-4 secretion. Furthermore, IL-4 increases MHC class II expression induced by IFN-γ in mast cells (53). This, in turn, is thought to increase the ability of mast cells to mobilize T cells locally through antigen presentation.…”

Adipose Tissue as a Dedicated Reservoir of Functional Mast Cell Progenitors

“…They are endowed with a large panel of pattern recognition receptors to identify pathogens and they are key effector cells in IgE-associated immune responses, including allergic disorders and certain protective immune responses to parasites [10]. Moreover, they can establish cognate interactions with different subsets of T lymphocytes [11,12].…”