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Blood, 1 March 2008, Vol. 111, No. 5, pp. 2497-2498. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nakae, S. Articles by Saito, H. Search for Related Content PubMed Articles by Nakae, S. Articles by Saito, H. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Comment on Kambayashi et al in the February 1 issue of Blood, page 1489 Mast cells and T-cell expansion Susumu Nakae, Keisuke Oboki, and Hirohisa Saito NATIONAL RESEARCH INSTITUTE FOR CHILD HEALTH AND DEVELOPMENT IgE/antigen-FcRI crosslinking promotes antigen internalization and apoptosis in mouse mast cells. Dendritic cells uptake the apoptotic mast cells carrying internalized antigens, and thus can efficiently present the antigens to memory T cells. Mast cells (MCs) are responsible for host defenses against bacterial, viral, and parasitic infection through the activation of complement-mediated or Toll-like receptor (TLR)–mediated innate immune responses and IgE/antigen-FcRI–mediated acquired immune responses.1 However, excessive or inappropriate MC activation also contributes to the development of certain allergic or autoimmune diseases, which are mediated by allergen- or autoantigen-specific effector T cells.1 MCs are capable of presenting antigens to T cells by direct cell-cell interaction through antigen-specific T-cell receptor (TCR) and major histocompatibility complex (MHC) class I– or class II–restricted mechanisms in vitro.1 Exosomes released from MCs, which contain MHC class II and antigen complexes, participate in antigen-specific T-cell expansion/activation independently of direct cell-cell contact between T cells and MCs in vitro.1 However, it has remained unclear whether MCs have such functions in vivo. In the February 1 issue of Blood, Kambayashi and coworkers provided a novel molecular mechanism for MHC class II–restricted, antigen-specific T-cell expansion/activation by murine bone marrow–derived cultured MCs (BMCMCs) in a series of well-designed and elegant experiments. Consistent with prior work,2 they demonstrated that naive BMCMCs showed poor antigen-presenting capabilities to CD4+ T cells from MHC class II–restricted and the ovalbumin (OVA)-specific TCR-transgenic (OTII) stain. However, MHC class II–deficient BMCMCs stimulated in advance with anti-OVA IgE and OVA were found to clearly facilitate OTII T-cell activation without further addition of OVA. In addition, IgE/antigen-FcRI crosslinking enhanced the internalization of IgE/antigen complexes in MCs, and induced MC apoptosis by down-modulating Bcl-XL expression. The authors also demonstrated that apoptotic MCs carrying intracellularly incorporated antigens were phagocytosed by dendritic cells (DCs). Then, DCs processed the MC-derived intracellular antigens, presented them to CD4+ T cells, and thus induced the expansion/activation of antigen-specific T cells (see figure). These findings suggest that MCs can work as antigen reservoirs and can act as "bridging cells" that transfer the antigen to potent antigen-presenting cells such as DCs. View larger version (46K): [in this window] [in a new window]   Role of MCs in IgE- and dendritic-cell–mediated antigen-specific T-cell expansion. (A) In a conventional antigen-presentation model, dendritic cells (DCs) incorporate antigens (Ags) and present antigen to naive T (TN) or memory T (TH2) cells. (B) In the MC-mediated, IgE-mediated, and DC-mediated antigen presentation model, IgE/antigen-FcRI crosslinking promotes antigen internalization and apoptosis in MCs. DCs then uptake the apoptotic MCs (aMCs) carrying internalized antigens, and thus can efficiently present the antigen to antigen-specific memory T cells.   MCs exist in close proximity with T cells in human tonsils3 as well as at the inflammatory sites in mice,2 and in close proximity with DCs in most tissues.4 In addition, MCs can migrate into draining lymph nodes from antigen entry sites.5 Based on the present work by Kambayashi and coworkers, it is possible that IgE/antigen-captured MCs become apoptotic in T-cell zones1 in secondary lymphoid tissues and/or at antigen-challenged inflammatory sites. Thus, DCs can present MC-derived antigens to "antigen-specific," that is, already antigen-sensitized, memory T helper cells. In contrast to a previous report indicating that MC-mediated T-cell activation is Ig/antigen-FcR independent,2 the findings of Kambayashi and colleagues indicate that MC-mediated T-cell activation is dependent on IgE, and thus it cannot be adopted for less/non-IgE–mediated diseases such as autoimmune disorders. Nevertheless, the present findings provide new insight into our understanding of the molecular mechanisms in-volved in the development of IgE- and MC-mediated allergic diseases. Footnotes Conflict-of-interest disclosure: H.S. received a grant from the National Institute of Biomedical Innovation. The other authors declare no competing financial interests. REFERENCES Galli SJ, Nakae S, Tsai M. Mast cells in the development of adaptive immune responses. Nat Immunol 2005; 6:135–142.[CrossRef][Medline] [Order article via Infotrieve] Nakae S, Suto H, Kakurai M, Sedgwick JD, Tsai M, Galli SJ. Mast cells enhance T cell activation: Importance of mast cell-derived TNF. Proc Natl Acad Sci U S A 2005; 102:6467–6472.[Abstract/Free Full Text] Kashiwakura J, Yokoi H, Saito H, Okayama Y. T cell proliferation by direct cross-talk between OX40 ligand on human mast cells and OX40 on human T cells: comparison of gene expression profiles between human tonsillar and lung-cultured mast cells. J Immunol 2004; 173:5247–5257.[Abstract/Free Full Text] Christy AL and Brown MA. The multitasking mast cell: positive and negative roles in the progression of autoimmunity. J Immunol 2007; 179:2673–2679.[Abstract/Free Full Text] Wang HW, Tedla N, Lloyd AR, Wakefield D, McNeil PH. Mast cell activation and migration to lymph nodes during induction of an immune response in mice. J Clin Invest 1998; 102:1617–1626.[Medline] [Order article via Infotrieve] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Indirect involvement of allergen-captured mast cells in antigen presentation Taku Kambayashi, Jan D. Baranski, Rebecca G. Baker, Tao Zou, Eric J. Allenspach, Jonathan E. Shoag, Peter L. Jones, and Gary A. Koretzky Blood 2008 111: 1489-1496. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Nakae, S. Articles by Saito, H. Search for Related Content PubMed Articles by Nakae, S. Articles by Saito, H. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?

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