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Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells.

Publication ,  Journal Article
Kiapour, N; Wu, B; Wang, Y; Seyedsadr, M; Kapoor, S; Zhang, X; Elzoheiry, M; Kasimoglu, E; Wan, Y; Markovic-Plese, S
Published in: J Immunol
July 1, 2022

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.

Duke Scholars

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

July 1, 2022

Volume

209

Issue

1

Start / End Page

49 / 56

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Multiple Sclerosis, Relapsing-Remitting
  • Multiple Sclerosis
  • Mice
  • Interleukin-17
  • Immunology
  • Forkhead Transcription Factors
  • Encephalomyelitis, Autoimmune, Experimental
  • Animals
  • Alemtuzumab
 

Citation

APA
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ICMJE
MLA
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Kiapour, N., Wu, B., Wang, Y., Seyedsadr, M., Kapoor, S., Zhang, X., … Markovic-Plese, S. (2022). Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells. J Immunol, 209(1), 49–56. https://doi.org/10.4049/jimmunol.2100176
Kiapour, Nazanin, Bing Wu, Yan Wang, Maryamsadat Seyedsadr, Sahil Kapoor, Xin Zhang, Manal Elzoheiry, Ezgi Kasimoglu, Yisong Wan, and Silva Markovic-Plese. “Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells.J Immunol 209, no. 1 (July 1, 2022): 49–56. https://doi.org/10.4049/jimmunol.2100176.
Kiapour N, Wu B, Wang Y, Seyedsadr M, Kapoor S, Zhang X, et al. Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells. J Immunol. 2022 Jul 1;209(1):49–56.
Kiapour, Nazanin, et al. “Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells.J Immunol, vol. 209, no. 1, July 2022, pp. 49–56. Pubmed, doi:10.4049/jimmunol.2100176.
Kiapour N, Wu B, Wang Y, Seyedsadr M, Kapoor S, Zhang X, Elzoheiry M, Kasimoglu E, Wan Y, Markovic-Plese S. Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells. J Immunol. 2022 Jul 1;209(1):49–56.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

July 1, 2022

Volume

209

Issue

1

Start / End Page

49 / 56

Location

United States

Related Subject Headings

  • T-Lymphocytes, Regulatory
  • Multiple Sclerosis, Relapsing-Remitting
  • Multiple Sclerosis
  • Mice
  • Interleukin-17
  • Immunology
  • Forkhead Transcription Factors
  • Encephalomyelitis, Autoimmune, Experimental
  • Animals
  • Alemtuzumab