Capacity of mouse mast cells to prime T cells and to induce specific antibody responses in vivo

Mouse, human and rat mast cells have been shown to express major histocompatibility complex II molecules and present antigens to specific T-cell hybridomas in vitro. The purpose of our investigation was to determine whether mouse mast cells are able to initiate specific immune responses in vivo. Induction of anti-dinitrophenyl (DNP) immunoglobulin G1 (IgG1) and IgG2a antibodies was performed by transferring ovalbumin (OVA)–DNP-pulsed bone marrow-derived mast cells (BMMC), B cells, or macrophages into naive mice which were boosted later with soluble antigen. Cultured spleen cells from immunized mice were tested for their cytokine content. Our data show that mast cells were by far better inducers of anti-DNP IgG1 antibodies than were B cells and macrophages. In contrast, anti-DNP IgG2a response induced by macrophages was much stronger than that obtained with mast cells whereas B cells were completely unable to elicit this response. In addition to a high index of cell proliferation, spleen cells from mast cell-injected mice produced more interferon-γ than those mice who received macrophages or B cells by two- to fivefold, and almost 10-fold, respectively. Mast cell-deficient W(f)/W(f) mice were compared with their normal +/+ littermates and with mast cell-reconstituted W(f)/W(f) mice to develop delayed-type hypersensitivity (DTH) reactions as well as humoral immune responses. Mast cell sufficient mice as well as mast cell-reconstituted W(f)/W(f) mice developed significantly increased DTH reactions (P = 0·02, and 0·03, repectively) and higher anti-OVA-specific antibody responses as compared with W(f)/W(f) mice. Our data suggest that mast cells have the potential to up-regulate both humoral and cellular immune responses in vivo

Mast cells enhance T cell activation: Importance of mast cell-derived TNF

Mast cells are not only important effector cells in immediate hypersensitivity reactions and immune responses to pathogens but also can contribute to T cell-mediated disorders. However, the mechanisms by which mast cells might influence T cells in such settings are not fully understood. We find that mast cells can enhance proliferation and cytokine production in multiple T cell subsets. Mast cell-dependent enhancement of T cell activation can be promoted by FcεRI-dependent mast cell activation, TNF production by both mast cells and T cells, and mast cell-T cell contact. However, at high concentrations of cells, mast cells can promote T cell activation independent of IgE or TNF. Finally, mast cells also can promote T cell activation by means of soluble factors. These findings identify multiple mechanisms by which mast cells can influence T cell proliferation and cytokine production

FcεRI-mediated antigen endocytosis turns interferon-γ-treated mouse mast cells from inefficient into potent antigen-presenting cells

Previous studies in our laboratory have shown that bone-marrow-derived mast cells (BMMC) could present immunogenic peptides, from soluble antigens endocytosed through fluid phase, only if they were subjected to a 48-hr treatment with interleukin-4 (IL-4) and granulocyte–macrophage colony-stimulating factor (GM-CSF). In contrast to GM-CSF, interferon-γ (IFN-γ) which highly upregulates major histocompatibility complex (MHC) class II expression, completely inhibits the generation of immunogenic peptides. We have used this model to study the role of FcεRI-mediated antigen internalization in the regulation of the antigen-presenting function of IFN-γ-treated mast cells. Here, we report that FcεRI can reverse the IFN-γ-treated mast cells from inefficient to highly efficient antigen-presenting cells. Inhibition of the antigen presenting capacity by piceatannol, a protein tyrosine kinase (PTK) syk inhibitor, indicates that this is an active process resulting from immunoglobulin E (IgE)–antigen–FcεRI engagement which involves tyrosines found in the immunoreceptor tyrosine-based activation motif (ITAM) embedded in the cytoplasmic tail of the FcεRI β and γ chains. Antigen-presenting function was also shown to require the activation of phosphatidyl inositol 3 (PI3) kinase, downstream of PTK syk phosphorylation, since this activity was completely blocked by wortmannin, a PI3 kinase inhibitor. These data suggest that signalling generated by FcεRI provides mast cells with IgE-mediated enhanced antigen presentation to T cells and emphasize a so far unknown immunoregulatory mast-cell function that might take place in inflammatory sites

Indirect involvement of allergen-captured mast cells in antigen presentation

It is generally thought that mast cells influence T-cell activation nonspecifically through the release of inflammatory mediators. In this report, we provide evidence that mast cells may also affect antigen-specific T-cell responses by internalizing immunoglobulin E–bound antigens for presentation to antigen-specific T cells. Surprisingly, T-cell activation did not require that mast cells express major histocompatibility complex class II, indicating that mast cells were not involved in the direct presentation of the internalized antigens. Rather, the antigen captured by mast cells is presented by other major histocompatibility complex class II+ antigen-presenting cells. To explore how this may occur, we investigated the fate of mast cells stimulated by antigen and found that FcϵRI crosslinking enhances mast cell apoptosis. Cell death by antigen-captured mast cells was required for efficient presentation because protection of mast cell death significantly decreased T-cell activation. These results suggest that mast cells may be involved in antigen presentation by acting as an antigen reservoir after antigen capture through specific immunoglobulin E molecules bound to their FcϵRI. This mechanism may contribute to how mast cells impact the development of T-cell responses

Global transformations of the state, governance and teachers’ labour: Putting Bernstein’s conceptual grammar to work

This paper presents and engages with Basil Bernstein’s rich conceptual grammar in order to generate a sociological account of the outcomes for teachers’ work, identity and social class, of strategic shifts in governance to the global scale. Our aim is to develop a two-way conversation between Bernstein’s conceptual grammar and how best to theorise the nature of the social regulation of teachers as a result of the dominance of the Organisation for Economic Cooperation and Development (OECD) in setting the rules for pedagogic governance of teachers through its Teaching and Learning International Survey (TALIS). We show that important functions for symbolic agents have been relocated to the economic arena away from the state, as well as being rescaled to sit within the governing ambit of the OECD. We also reflect on the prominence of constructivism in TALIS as a preferred pedagogy and the eschewing of disciplinary knowledge as the basis of expertise. We ask what this new market identity means for teacher knowledge, consciousness, identity, the division of labour, and the social base. </jats:p