Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells
| Autor: | Nazanin Kiapour, Bing Wu, Yan Wang, Maryamsadat Seyedsadr, Sahil Kapoor, Xin Zhang, Manal Elzoheiry, Ezgi Kasimoglu, Yisong Wan, Silva Markovic-Plese |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 209:49-56 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The objective of this study is to determine the mechanism of action of anti-CD52 mAb treatment in patients with relapsing-remitting multiple sclerosis (RRMS). Experimental autoimmune encephalomyelitis (EAE), an animal model of the disease, was used to address the role of T regulatory cells (Tregs) in the anti-CD52 mAb–induced suppression of the disease. In vitro studies on PBMCs from RRMS patients and matched healthy controls determined the effect of IL-7 on the expansion of CD4+CD25+CD127− Tregs and induction of their suppressive phenotype. This study using EAE animal models of MS has shown that mouse anti-CD52 mAb suppression of clinical disease was augmented by coadministration of IL-7 and partially reversed by anti-IL-7 mAb. In vitro human studies showed that IL-7 induced expansion of CD4+CD25+CD127− Tregs and increased their FOXP3, GITIR, CD46, CTLA-4, granzyme B, and perforin expression. Anti-CD52 mAb treatment of mice with relapsing-remitting EAE induced expansion of Foxp3+CD4+ Tregs and the suppression of IL-17A+CD4+ and IFN-γ+CD4+ cells in peripheral immune organs and CNS infiltrates. The effect was detected immediately after the treatment and maintained over long-term follow-up. Foxp3+CD4+ Treg-mediated suppression of IL-17A+CD4+ and IFN-γ+CD4+ cells in the spinal cord infiltrates was reversed after inducible Foxp3 depletion. Our results demonstrated that the therapeutic effect of U.S. Food and Drug Administration–approved anti-CD52 mAb is dependent on the presence of Tregs. |
| Databáze: | OpenAIRE |
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