B7-1 mediated costimulation regulates pancreatic autoimmunity
| Autor: | Miyuki Azuma, Nora Sarvetnick, Deepak Yadav, Cody Fine |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cell Survival Immunology Programmed Cell Death 1 Receptor Priming (immunology) Autoimmunity Nod Biology CD8-Positive T-Lymphocytes medicine.disease_cause Lymphocyte Activation Article Islets of Langerhans Mice Antigen CD28 Antigens medicine Animals Molecular Biology Pancreas Mice Knockout geography geography.geographical_feature_category Effector Islet Antigens Differentiation Thymocyte Diabetes Mellitus Type 1 B7-1 Antigen Female CD8 |
| Zdroj: | Molecular immunology. 44(10) |
| ISSN: | 0161-5890 |
| Popis: | Costimulation by B7-1 and B7-2 molecules results in divergent biological effects. This is particularly striking in the NOD mouse, since the lack of B7-2 leads to complete protection from autoimmunity, whereas the B7-1 deficiency causes exacerbation of disease. We tested the hypothesis that B7-1 costimulation suppresses pancreatic autoimmunity. We describe that the lack of B7-1 not only causes aberrant thymocyte maturation but also significantly enhances expansion, survival, and effector function of islet specific T cells in periphery. We also observed a significant reduction in the proportion of T-regulatory (T-regs) cells. Immunophenotypic analysis of T and APCs revealed a significantly lower frequency of T cells expressing the negative costimulatory receptor PD-1 in B7-1KO mice whereas the proportion of B7-H1 positive APCs was found to be significantly higher. Blocking studies in B7-1KO mice suggest that B7-H1 provides negative signals for anti islet CD4 and CD8 T cell expansion but is differentially required for their priming. Our data demonstrate that deficiency of B7-1 mediated costimulation causes multitude of immunological defects, which involve reduction in T-regs and a concomitant enhancement of expansion, survival and effector potential of auto reactive T cells. |
| Databáze: | OpenAIRE |
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