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The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice.

Jun, HS; Yoon, CS; Zbytnuik, L; van Rooijen, N; Yoon, JW
The Journal of experimental medicine, 189(2):347-358, 1999
Journal Title
The Journal of experimental medicine
We have shown previously that the inactivation of macrophages in nonobese diabetic (NOD) mice results in the prevention of diabetes; however, the mechanisms involved remain unknown. In this study, we found that T cells in a macrophage-depleted environment lost their ability to differentiate into beta cell-cytotoxic T cells, resulting in the prevention of autoimmune diabetes, but these T cells regained their beta cell-cytotoxic potential when returned to a macrophage-containing environment. To learn why T cells in a macrophage-depleted environment lose their ability to kill beta cells, we examined the islet antigen-specific immune response and T cell activation in macrophage-depleted NOD mice. There was a shift in the immune balance, a decrease in the T helper cell type 1 (Th1) immune response, and an increase in the Th2 immune response, due to the reduced expression of the macrophage-derived cytokine IL-12. As well, there was a deficit in T cell activation, evidenced by significant decreases in the expression of Fas ligand and perforin. The administration of IL-12 substantially reversed the prevention of diabetes in NOD mice conferred by macrophage depletion. We conclude that macrophages play an essential role in the development and activation of beta cell-cytotoxic T cells that cause beta cell destruction, resulting in autoimmune diabetes in NOD mice.
MeSH terms
AnimalsAutoimmunity/immunology*Cell Differentiation/immunologyClodronic Acid/pharmacologyCytotoxicity, Immunologic/immunologyDiabetes Mellitus/geneticsDiabetes Mellitus/immunologyFas Ligand ProteinFemaleInterleukin-12/pharmacologyIslets of Langerhans/drug effectsIslets of Langerhans/immunologyMacrophages/immunology*Membrane Glycoproteins/metabolismMiceMice, Inbred NODPancreas/drug effectsPancreas/pathologyPerforinPore Forming Cytotoxic ProteinsSpleen/immunologyT-Lymphocytes/immunologyTissue Transplantation
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Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
AJOU Authors
윤, 지원
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