FcR interactions do not play a major role in inhibition of experimental autoimmune encephalomyelitis by anti-CD154 monoclonal antibodies
| Autor: | Ellen Garber, Wouter van Rijs, Linda C. Burkly, Janine Ferrant, Lex Nagelkerken, Inge Haspels, Frederick R. Taylor, Hess Donna M, Bep Blauw |
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| Rok vydání: | 2004 |
| Předmět: |
Proteolipid protein 1
Encephalomyelitis Autoimmune Experimental Glycosylation medicine.drug_class T-Lymphocytes Immunology CD40 Ligand Receptors Fc Monoclonal antibody Mice immune system diseases medicine Immunology and Allergy Animals CD154 Receptor Myelin Proteolipid Protein B-Lymphocytes CD40 biology Chemistry Experimental autoimmune encephalomyelitis Antibodies Monoclonal medicine.disease Peptide Fragments Myelin proteolipid protein biology.protein Female Antibody |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 173(2) |
| ISSN: | 0022-1767 |
| Popis: | It has been demonstrated that anti-CD154 mAb treatment effectively inhibits the development of experimental autoimmune encephalomyelitis (EAE). However, although it appears to prevent the induction of Th1 cells and reactivation of encephalitogenic T cells within the CNS, little information is available regarding the involvement of alternative mechanisms, nor has the contribution of Fc effector mechanisms in this context been addressed. By contrast, efficacy of anti-CD154 mAbs in models of allotransplantation has been reported to involve long-term unresponsiveness, potentially via activation of T regulatory cells, and recently was reported to depend on Fc-dependent functions, such as activated T cell depletion through FcγR or complement. In this study we demonstrate that anti-CD154 mAb treatment inhibits EAE development in SJL mice without apparent long-term unresponsiveness or active suppression of disease. To address whether the mechanism of inhibition of EAE by anti-CD154 mAb depends on its Fc effector interactions, we compared an anti-CD154 mAb with its aglycosyl counterpart with severely impaired FcγR binding and reduced complement binding activity with regard to their ability to inhibit clinical signs of EAE and report that both forms of the Ab are similarly protective. This observation was largely confirmed by the extent of leukocyte infiltration of the CNS; however, mice treated with the aglycosyl form may display slightly more proteolipid protein 139-151-specific immune reactivity. It is concluded that FcR interactions do not play a major role in the protective effect of anti-CD154 mAb in the context of EAE, though they may contribute to the full abrogation of peripheral peptide-specific lymphocyte responses. Chemicals / CAS: Antibodies, Monoclonal; CD40 Ligand, 147205-72-9; Myelin Proteolipid Protein; Peptide Fragments; proteolipid protein 139-151; Receptors, Fc |
| Databáze: | OpenAIRE |
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