Abstract
While examining the therapeutic value of anti-CD52 antibody against EAE/MS, we identified a unique subset of CD39+ Tregs in repopulating GALT tissues, a major lymphoid reservoir, which was accompanied by amelioration of disease. Furthermore, anti-CD52 treatment leads to increased expression of BDNF, IL-10, and SMAD3 in the brains of EAE mice. This condition is associated with suppression of IL-17, a critical inflammatory factor in EAE/MS progression. Additionally, we found elevated levels of CD4+CD39+ Tregs in PBMCs of RRMS patients treated with humanized anti-CD52 mAb. Thus, anti-CD52 can affect multiple immune mediated pathways involved in the pathogenesis of EAE/MS.
Keywords:
Anti-CD52 mAb; CD39+ T regulatory cells; Cytokine; Experimental autoimmune encephalomyelitis; Multiple sclerosis; Therapeutic.
Copyright © 2016. Published by Elsevier B.V.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use*
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Antigens, CD / immunology
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Antigens, CD / metabolism*
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Antigens, Neoplasm / immunology
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Antigens, Neoplasm / metabolism*
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Apyrase / immunology
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Apyrase / metabolism*
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism*
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CD52 Antigen
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Cytokines / immunology
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Cytokines / metabolism*
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Encephalomyelitis, Autoimmune, Experimental / drug therapy
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / metabolism*
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Forkhead Transcription Factors / immunology
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Forkhead Transcription Factors / metabolism*
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Glycoproteins / antagonists & inhibitors
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Glycoproteins / immunology
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Glycoproteins / metabolism*
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Humans
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Mice
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Mice, Inbred C57BL
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Multiple Sclerosis / drug therapy
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Multiple Sclerosis / immunology
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Multiple Sclerosis / metabolism
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Treatment Outcome
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Neoplasm
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CD52 Antigen
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CD52 protein, human
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Cytokines
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Glycoproteins
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Apyrase
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CD39 antigen