Different diabetogenic potential of autoaggressive CD8+ clones associated with IFN-gamma-inducible protein 10 (CXC chemokine ligand 10) production but not cytokine expression, cytolytic activity, or homing characteristics
| Autor: | Urs Christen, Anne Cooke, Matthias von Herrath, Mette Ejrnaes, Birgitte K. Michelsen, Nicoline Videbæk |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cytotoxicity
Immunologic medicine.medical_treatment Immunology Islets of Langerhans Transplantation Epitopes T-Lymphocyte Mice SCID Biology CD8-Positive T-Lymphocytes Islets of Langerhans Mice Cell Movement Mice Inbred NOD Cell Line Tumor medicine Immunology and Allergy Cytotoxic T cell Animals Insulin Cells Cultured NOD mice Type 1 diabetes Glutamate Decarboxylase medicine.disease Peptide Fragments Clone Cells Chemokine CXCL10 Isoenzymes Cytolysis medicine.anatomical_structure Cytokine Diabetes Mellitus Type 1 Cytokines Female Chemokines Pancreas Chemokines CXC CD8 Injections Intraperitoneal |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 174(5) |
| ISSN: | 0022-1767 |
| Popis: | Type 1 diabetes mellitus is an autoimmune disease characterized by T cell-mediated destruction of the insulin-producing β cells in the islets of Langerhans. From studies in animal models, CD8+ T cells recognizing autoantigens such as islet-specific glucose-6-phosphatase catalytic subunit-related protein, insulin, or glutamic acid decarboxylase (GAD) are believed to play important roles in both the early and late phases of β cell destruction. In this study, we investigated the factors governing the diabetogenic potential of autoreactive CD8+ clones isolated from spleens of NOD mice that had been immunized with GAD65515–524 or insulin B-chain15–23 peptides. Although these two clones were identical in most phenotypic and functional aspects, for example cytokine production and killing of autologous β cells, they differed in the expression of IFN-γ-inducible protein-10, which was only produced at high levels by the insulin-specific clone, but not by the GAD65-specific clone, and other autoantigen-specific nonpathogenic CD8 T cell clones. Interestingly, upon i.p. injection into neonatal mice, only the insulin B-chain15–23-reactive CD8+ T clone accelerated diabetes in all recipients after 4 wk, although both insulin- and GAD-reactive clones homed to pancreas and pancreatic lymph nodes with similar kinetics. Diabetes was associated with increased pancreatic T cell infiltration and, in particular, recruitment of macrophages. Thus, secretion of IFN-γ-inducible protein-10 by autoaggressive CD8+ lymphocytes might determine their diabetogenic capacity by affecting recruitment of cells to the insulitic lesion. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|