Anti-CD40L accelerates renal disease and adenopathy in MRL-lpr mice in parallel with decreased thymocyte apoptosis
| Autor: | J Q, Russell, T, Mooney, P L, Cohen, B, MacPherson, R J, Noelle, R C, Budd |
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| Rok vydání: | 1998 |
| Předmět: |
Mice
Inbred MRL lpr Membrane Glycoproteins Receptors Antigen T-Cell alpha-beta CD40 Ligand Antibodies Monoclonal Apoptosis Thymus Gland Ligands Survival Analysis Mice Glomerulonephritis T-Lymphocyte Subsets Animals Female Lymph Nodes CD40 Antigens Lymphatic Diseases Injections Intraperitoneal Autoantibodies |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 161(2) |
| ISSN: | 0022-1767 |
| Popis: | The CD40/CD40L (CD40 ligand) axis regulates several interactions between T cells and B cells. Blocking of CD40 engagement by CD40L inhibits Ig class switch by B cells as well as diminishes T cell response to an immunizing Ag. For these reasons, disruption of CD40/CD40L interactions by anti-CD40L administration or by genetic disruption of CD40L has ameliorated a variety of autoimmune conditions. More recent findings suggest that a direct signal can be transmitted to T cells via their expressed CD40L, which can costimulate proliferation with CD3 or promote germinal center formation. It is therefore possible that treatment with anti-CD40L Ab might produce a different outcome than observed in genetically CD40L-deficient mice. In this regard, we observe that in contrast to the genetic deletion of CD40L in MRL-lpr mice, which diminishes autoimmune disease but has little effect on adenopathy, administration of anti-CD40L to MRL-lpr mice accelerates both of these parameters. This difference appears to result from anti-CD40L actively delivering a signal that inhibits T cell apoptosis in lpr mice. This was confirmed by in vitro studies demonstrating that CD40L cross-linking on lpr thymocytes inhibited apoptosis and surface TCR down-modulation induced by CD3 ligation. |
| Databáze: | OpenAIRE |
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