Beta cells transfer vesicles containing insulin to phagocytes for presentation to T cells.
Beta cells from nondiabetic mice transfer secretory vesicles to phagocytic cells. The passage was shown in culture studies where the transfer was probed with CD4 T cells reactive to insulin peptides. Two sets of vesicles were transferred, one containing insulin and another containing catabolites of insulin. The passage required live beta cells in a close cell contact interaction with the phagocytes. It was increased by high glucose concentration and required mobilization of intracellular Ca2+. Live images of beta cell-phagocyte interactions documented the intimacy of the membrane contact and the passage of the granules. The passage was found in beta cells isolated from islets of young nonobese diabetic (NOD) mice and nondiabetic mice as well as from nondiabetic humans. Ultrastructural analysis showed intraislet phagocytes containing vesicles having the distinct morphology of dense-core granules. These findings document a process whereby the contents of secretory granules become available to the immune system.
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Anthony N
AN
Vomund
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Bernd H
BH
Zinselmeyer
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Jing
J
Hughes
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Boris
B
Calderon
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Carolina
C
Valderrama
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Stephen T
ST
Ferris
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Xiaoxiao
X
Wan
Division of Endocrinology, Metabolism and Lipid Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Kohsuke
K
Kanekura
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110;
Javier A
JA
Carrero
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; Division of Endocrinology, Metabolism and Lipid Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110.
Fumihiko
F
Urano
Division of Immunobiology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110; unanue@wustl.edu.
Emil R
ER
Unanue
D000328:Adult; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000091342:Endoplasmic Reticulum Chaperone BiP; D000067128:Extracellular Vesicles / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000276:immunology* / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D036641:Microscopy, Fluorescence, Multiphoton; D010586:Phagocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051742:Transcription Factor CHOP / Q000235:genetics
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007328:Insulin; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D051742:Transcription Factor CHOP; D004533:Egtazic Acid; D005947:Glucose; D002118:Calcium
autoimmune diabetes; autoimmunity; insulin reactivity; insulin-reactive T cells