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* Abramson Family Cancer Research Institute,
Department of Pathology and Laboratory Medicine,
Department of Medicine, University of Pennsylvania School of Medicine, and
The Wistar Institute, Philadelphia, PA 19104
In addition to their well-established role as regulators of allergic response, recent evidence supports a role for mast cells in influencing the outcome of physiologic and pathologic T cell responses. One mechanism by which mast cells (MCs) influence T cell function is indirectly through secretion of various cytokines. It remains unclear, however, whether MCs can directly activate T cells through Ag presentation, as the expression of MHC class II by MCs has been controversial. In this report, we demonstrate that in vitro stimulation of mouse MCs with LPS and IFN-
induces the expression of MHC class II and costimulatory molecules. Although freshly isolated peritoneal MCs do not express MHC class II, an in vivo inflammatory stimulus increases the number of MHC class II-positive MCs in situ. Expression of MHC class II granted MCs the ability to process and present Ags directly to T cells with preferential expansion of Ag-specific regulatory T cells over naive T cells. These data support the notion that, in the appropriate setting, MCs may regulate T cell responses through the direct presentation of Ag.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by grants from the Sandler Program for Asthma Research and from the National Institutes of Health.
2 Address correspondence and reprint requests to Dr. Gary A. Koretzky, Abramson Family Cancer Research Institute, University of Pennsylvania, BRB II/III Room 415, 421 Curie Boulevard, Philadelphia PA 19104-6160. E-mail address: koretzky{at}mail.med.upenn.edu
3 Abbreviations used in this paper: MC, mast cell; MHC-II, MHC class II; Treg, regulatory T cell; PD-L1, programmed death ligand 1; BMMC, bone marrow-derived MC; DC, dendritic cell; LN, lymph node; HA, hemagglutinin; TNP, trinitrophenyl; WT, wild type.
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