Mast Cell-Mediated Antigen Presentation Regulates CD8+ T Cell Effector Functions

• Published in: Immunity (Cambridge, Mass.) Vol. 31; no. 4; pp. 665 - 676
• Main Authors: Stelekati, Erietta, Bahri, Rajia, D'Orlando, Orietta, Orinska, Zane, Mittrücker, Hans-Willi, Langenhaun, Rabea, Glatzel, Markus, Bollinger, Annalena, Paus, Ralf, Bulfone-Paus, Silvia
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.10.2009; Elsevier Limited
• Subjects: Adoptive Transfer; Animals; Antigen Presentation - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - microbiology; Cell adhesion & migration; Cell Degranulation - immunology; CELLIMMUNO; Chemokine CCL3 - biosynthesis; Chemokine CCL3 - immunology; Coculture Techniques; Cross-Priming - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Encephalomyelitis, Autoimmune, Experimental - pathology; Glycoproteins - immunology; Granzymes - immunology; Granzymes - metabolism; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class I - metabolism; Immune system; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukin-2 - biosynthesis; Interleukin-2 - immunology; Listeria monocytogenes - immunology; Listeriosis - immunology; Listeriosis - microbiology; Mast Cells - immunology; Mast Cells - metabolism; Mast Cells - microbiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; MOLIMMUNO; Myelin-Oligodendrocyte Glycoprotein; Osteopontin - immunology; Osteopontin - metabolism; Ovalbumin - immunology; Peptide Fragments - immunology; Peptides; T cell receptors; Tumor Necrosis Factor Receptor Superfamily, Member 9 - immunology; Tumor Necrosis Factor Receptor Superfamily, Member 9 - metabolism; MOLIMMUNO; CELLIMMUNO
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2009.08.022

The characteristics, importance, and molecular requirements for interactions between mast cells (MCs) and CD8+ T cells have not been elucidated. Here, we demonstrated that MCs induced antigen-specific CD8+ T cell activation and proliferation. This process required direct cell contact and MHC class I-dependent antigen cross-presentation by MCs and induced the secretion of interleukin-2, interferon-γ, and macrophage inflammatory protein-1α by CD8+ T cells. MCs regulated antigen-specific CD8+ T cell cytotoxicity by increasing granzyme B expression and by promoting CD8+ T cell degranulation. Because MCs also upregulated their expression of costimulatory molecules (4-1BB) and released osteopontin upon direct T cell contact, MC-T cell interactions probably are bidirectional. In vivo, adoptive transfer of antigen-pulsed MCs induced MHC class I-dependent, antigen-specific CD8+ T cell proliferation, and MCs regulated CD8+ T cell-specific priming in experimental autoimmune encephalomyelitis. Thus, MCs are important players in antigen-specific regulation of CD8+ T cells.