A novel form of self tolerance dictated in the thymus of transgenic mice with autoreactive TCR α and β chain genes
| Autor: | Man-Jong Bae, Shuichi Kubo, Tomio Tada, Naoki Takeda, Shinichi Aizawa, Kahoko Hashimoto, Taeko Yokochi, Toshinori Takayama, Yoshihiro Asano, H Kishimoto, Makoto Furutani-Seiki |
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| Rok vydání: | 1994 |
| Předmět: |
Receptors
Antigen T-Cell alpha-beta T-Lymphocytes Transgene Immunology Mice Transgenic Thymus Gland Biology Lymphocyte Activation medicine.disease_cause Autoantigens Clonal deletion Immune tolerance Autoimmunity Mice Antigens CD medicine Animals Immunology and Allergy Antigen-presenting cell T-cell receptor H-2 Antigens General Medicine T lymphocyte Flow Cytometry Clone Cells Cell biology Self Tolerance biology.protein Antibody |
| Zdroj: | International Immunology. 6:593-602 |
| ISSN: | 1460-2377 0953-8178 |
| Popis: | Transgenic (TG) mice with TCR alpha and beta chain genes from a CD4-dependent auto-I-Ak reactive T cell clone were generated. H-2k TG mice had a large number of thymic and splenic CD4 T cells expressing the autoreactive TCR without manifestation of autoimmunity. The cells were not anergic, as they could respond to autologous antigen presenting cells and anti-TCR antibodies in vitro to proliferate and to produce interleukins. Various degrees of down-regulation of CD2 and CD44 was observed in TG mice, indicating the presence of a defective co-stimulatory process in TG T cells. These features indicate that the self tolerance in autoreactive TCR TG mice is due not to clonal deletion and anergy but to a novel mechanism where T cells cannot sufficiently respond to normally existing self ligand in vivo. That such an in vivo unresponsiveness of autoreactive T cells is dictated in the thymus during CD4 T cell differentiation atypical form of positive selection of autoreactive T cells was suggested by the abnormal surface expression of CD69 and HSA. |
| Databáze: | OpenAIRE |
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