Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
J Immunol ; 176(8): 4730-9, 2006 Apr 15.
Article in English | MEDLINE | ID: mdl-16585566

ABSTRACT

Adaptive regulatory T cells that develop from naive CD4 cells in response to exposure to Ag can act as immunotherapeutic agents to control immune responses. We show that effectors generated from murine islet-specific CD4 cells by TCR stimulation with IL-2 and TGF-beta1 have potent suppressive activity. They prevent spontaneous development of type 1 diabetes in NOD mice and inhibit development of pancreatic infiltrates and disease onset orchestrated by Th1 effectors. These regulatory T cells do not require innate CD25+ regulatory cells for generation or function, nor do they share some characteristics typically associated with them, including expression of CD25. However, the adaptive population does acquire the X-linked forkhead/winged helix transcription factor, FoxP3, which is associated with regulatory T cell function and maintains expression in vivo. One mechanism by which they may inhibit Th1 cells is via FasL-dependent cytotoxicity, which occurs in vitro. In vivo, they eliminate Th1 cells in lymphoid tissues, where Fas/FasL interactions potentially play a role because Th1 cells persist when this pathway is blocked. The results suggest that adaptive regulatory CD4 cells may control diabetes in part by impairing the survival of islet-specific Th1 cells, and thereby inhibiting the localization and response of autoaggressive T cells in the pancreatic islets.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Diabetes Mellitus, Type 1/immunology , Islets of Langerhans/immunology , Th1 Cells/immunology , Adoptive Transfer , Animals , Antigens , CD4-Positive T-Lymphocytes/drug effects , Cytotoxicity, Immunologic , Diabetes Mellitus, Type 1/prevention & control , Fas Ligand Protein , Female , In Vitro Techniques , Interleukin-2/pharmacology , Membrane Glycoproteins/metabolism , Mice , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Mice, Transgenic , Transforming Growth Factor beta/pharmacology , Transforming Growth Factor beta1 , Tumor Necrosis Factors/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...