| Autor: |
Eric Muraille, Andris, F., Pajak, B., Wissing, K. M., Smedt, T., Desalle, F., Goldman, M., Alegre, M. -L, Urbain, J., Moser, M., Leo, O. |
| Přispěvatelé: |
Clinical sciences, Faculty of Law and Criminology |
| Jazyk: |
angličtina |
| Rok vydání: |
1999 |
| Předmět: |
|
| Zdroj: |
Scopus-Elsevier |
| Popis: |
Antibodies against CD3epsilon are widely used as immunosuppressive agents. Although it is generally assumed that these reagents exert their immunomodulatory properties by inducing T-cell deletion and/or inactivation, their precise mechanism of action remains to be elucidated. Using a murine model, we demonstrate in this report that administration of anti-CD3epsilon antibodies causes the migration and maturation of dendritic cells (DC) in vivo, as determined by immunohistochemical analysis. This maturation/migration process was followed by selective loss of splenic DC, which resulted in a selective inhibition of antigen-presenting cell (APC) functions in vitro. Spleen cells from anti-CD3epsilon-treated animals were unable to productively stimulate naive alloreactive T cells and Th1-like clones in response to antigen, while retaining the ability to present antigen to a T-cell hybridoma and Th2 clones. Anti-CD3epsilon treatment was found to induce a selective deficiency in the ability of spleen cells to produce bioactive interleukin-12 in response to CD40 stimulation. APC dysfunction was not observed when nonmitogenic forms of anti-CD3epsilon antibodies were used, suggesting that splenic DC loss was a consequence of in vivo T-cell activation. Nonmitogenic anti-CD3epsilon monoclonal antibodies were found to be less immunosuppressive in vivo, raising the possibility that APC dysfunction contributes to anti-CD3epsilon-induced immunomodulation. Collectively, these data suggest a novel mechanism by which mitogenic anti-CD3epsilon antibodies downregulate immune responses. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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