Mast cell-mediated antigen presentation regulates CD8+ T cell effector functions.
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-gamma, and macrophage inflammatory protein-1alpha 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.
Stelekati
Erietta
E
Department of Immunology and Cell Biology, Research Center Borstel, D-23845 Borstel, Germany.
Bahri
Rajia
R
D'Orlando
Orietta
O
Orinska
Zane
Z
Mittrücker
Hans-Willi
HW
Langenhaun
Rabea
R
Glatzel
Markus
M
Bollinger
Annalena
A
Paus
Ralf
R
Bulfone-Paus
Silvia
S
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015550:Cell Degranulation / Q000276:immunology; D054405:Chemokine CCL3 / Q000096:biosynthesis / Q000276:immunology; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006023:Glycoproteins / Q000276:immunology; D053804:Granzymes / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D063308:Myelin-Oligodendrocyte Glycoprotein; D053495:Osteopontin / Q000276:immunology / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology / Q000378:metabolism
D054405:Chemokine CCL3; D006023:Glycoproteins; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D063308:Myelin-Oligodendrocyte Glycoprotein; C110366:OVA-8; D010446:Peptide Fragments; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; C445081:myelin oligodendrocyte glycoprotein (35-55); D053495:Osteopontin; D007371:Interferon-gamma; D010047:Ovalbumin; D053804:Granzymes