Alteration of CD39+Foxp3+ CD4 T cell and cytokine levels in EAE/MS following anti-CD52 treatment

J Neuroimmunol. 2017 Feb 15:303:22-30. doi: 10.1016/j.jneuroim.2016.12.010. Epub 2016 Dec 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism*
  • Apyrase / immunology
  • Apyrase / metabolism*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • CD52 Antigen
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism*
  • Glycoproteins / antagonists & inhibitors
  • Glycoproteins / immunology
  • Glycoproteins / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / metabolism
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Neoplasm
  • CD52 Antigen
  • CD52 protein, human
  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Glycoproteins
  • Apyrase
  • CD39 antigen