Altered functional and biochemical response by CD8+ T cells that remain after tolerance
| Autor: | Valérie C. Asensio, Pankaj Tailor, Iain L. Campbell, Judith A. Biggs, Anwar Murtaza, C. Thomas Nugent, Linda A. Sherman |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cytotoxicity
Immunologic Immunology Clone (cell biology) Mice Transgenic chemical and pharmacologic phenomena Biology Ligands Diabetes Mellitus Experimental Immunophenotyping Mice Antigen Immune Tolerance Animals Immunology and Allergy Cytotoxic T cell Phosphorylation ZAP-70 Protein-Tyrosine Kinase T-cell receptor hemic and immune systems General Medicine T lymphocyte Protein-Tyrosine Kinases Molecular biology Clone Cells Mice Inbred C57BL Tolerance induction CTL Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Signal Transduction T-Lymphocytes Cytotoxic |
| Zdroj: | International Immunology. 13:1085-1093 |
| ISSN: | 1460-2377 0953-8178 |
| Popis: | To further define the molecular basis of tolerance to a peripherally expressed antigen we have correlated differences in functional capacity with biochemical events in hemagglutinin (HA)-specific cytotoxic T lymphocyte (CTL) clones derived either from a conventional B10.D2 mouse that is not tolerant to HA (D2 Clone 6) or from an InsHA mouse that is tolerant to HA (InsHA Clone 12). D2 Clone 6, but not InsHA Clone 12, triggers diabetes following in vivo transfer into irradiated InsHA hosts. This diabetogenic clone shows complete and sustained phosphorylation of TCR zeta chain and ZAP-70 following stimulation with HA-pulsed antigen-presenting cells. In contrast, InsHA Clone 12 showed only partial phosphorylation of TCR zeta and no phosphorylation of ZAP-70. There was no defect in activation or recruitment of Lck to the TCR complex in both the clones following stimulation with the cognate antigen. This deficiency in the proximal signaling in the InsHA Clone 12 could be overcome by increasing the strength of signal through the CD3-TCR complex, indicating that the signaling machinery of InsHA Clone 12 was functional. These data demonstrate that the HA-responsive CD8(+) T cells that can be retrieved from InsHA mice after tolerance induction respond to HA as a partial agonist/antagonist. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|