Relative diabetogenic properties of islet-specific Tc1 and Tc2 cells in immunocompetent hosts
| Autor: | Nadège Bercovici, Karine Goude, Christophe Combadière, Karine Bailly, Roland S. Liblau, Nathalie Pardigon, Csaba Vizler, Agnès Heurtier |
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| Přispěvatelé: | CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biologie Moléculaire du Gène, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by Agence Nationale de la Recherches sur le SIDA, Fondation de France, and Institut National de la Santé et de la Recherche Médicale., Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
MESH: T-Lymphocyte Subsets/transplantation
Adoptive cell transfer MESH: Diabetes Mellitus Type 1/pathology Epitopes T-Lymphocyte Hemagglutinin Glycoproteins Influenza Virus CD8-Positive T-Lymphocytes MESH: Promoter Regions Genetic/immunology medicine.disease_cause Lymphocyte Activation [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity Autoimmunity Mice MESH: Pancreas/pathology 0302 clinical medicine Cell Movement T-Lymphocyte Subsets MESH: Islets of Langerhans/immunology Tumor Cells Cultured Immunology and Allergy Cytotoxic T cell Insulin MESH: Animals Promoter Regions Genetic Cells Cultured 0303 health sciences Mice Inbred BALB C geography.geographical_feature_category MESH: Cell Movement/genetics MESH: Diabetes Mellitus Type 1/immunology MESH: Epitopes T-Lymphocyte/immunology MESH: CD8-Positive T-Lymphocytes/transplantation Cell Differentiation Islet Adoptive Transfer 3. Good health MESH: CD8-Positive T-Lymphocytes/immunology Interleukin 12 MESH: Diabetes Mellitus Type 1/genetics MESH: Cells Cultured endocrine system MESH: Rats MESH: Mice Transgenic Immunology MESH: Mice Inbred BALB C MESH: Cell Movement/immunology Mice Transgenic Biology MESH: CD8-Positive T-Lymphocytes/pathology 03 medical and health sciences Islets of Langerhans MESH: Lymphocyte Activation/genetics MESH: T-Lymphocyte Subsets/immunology medicine Animals MESH: Tumor Cells Cultured MESH: Insulin/genetics Pancreas MESH: Mice MESH: T-Lymphocyte Subsets/pathology 030304 developmental biology geography CD40 MESH: Diabetes Mellitus Type 1/etiology MESH: Islets of Langerhans/pathology MESH: Cell Differentiation/genetics In vitro Rats MESH: Adoptive Transfer Diabetes Mellitus Type 1 MESH: Pancreas/immunology MESH: Hemagglutinin Glycoproteins Influenza Virus/genetics MESH: Cell Differentiation/immunology biology.protein CD8 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, 2000, 165 (11), pp.6314-21. ⟨10.4049/jimmunol.165.11.6314⟩ Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2000, 165 (11), pp.6314-21. ⟨10.4049/jimmunol.165.11.6314⟩ ResearcherID |
| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.165.11.6314⟩ |
| Popis: | CD8+ T cells are important effectors, as well as regulators, of organ-specific autoimmunity. Compared with Tc1-type CD8+ cells, Tc2 cells have impaired anti-viral and anti-tumor effector functions, although no data are yet available on their pathogenic role in autoimmunity. Our aim was to explore the role of autoreactive Tc1 and Tc2 cells in autoimmune diabetes. We set up an adoptive transfer model in which the recipients were transgenic mice expressing influenza virus hemagglutinin (HA) specifically in their pancreatic β islet cells (rat insulin promoter-HA mice) and islet-specific Tc1 and Tc2 cells were generated in vitro from HA-specific CD8+ cells of TCR transgenic mice (CL4-TCR mice). One million Tc1 cells, differentiated in vitro in the presence of IL-12, transferred diabetes in 100% of nonirradiated adult rat insulin promoter-HA recipients; the 50% diabetogenic dose was 5 × 105. Highly polarized Tc2 cells generated in the presence of IL-4, IL-10, and anti-IFN-γ mAb had a relatively low, but definite, diabetogenic potential. Thus, 5 × 106 Tc2 cells caused diabetes in 6 of 18 recipients, while the same dose of naive CD8+ cells did not cause diabetes. Looking for the cause of the different diabetogenic potential of Tc1 and Tc2 cells, we found that Tc2 cells are at least as cytotoxic as Tc1 cells but their accumulation in the pancreas is slower, a possible consequence of differential chemokine receptor expression. The diabetogenicity of autoreactive Tc2 cells, most likely caused by their cytotoxic activity, precludes their therapeutic use as regulators of autoimmunity. |
| Databáze: | OpenAIRE |
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