Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis

J Immunol. 2013 Dec 15;191(12):5867-74. doi: 10.4049/jimmunol.1301926. Epub 2013 Nov 6.


Alemtuzumab (anti-CD52 mAb) provides long-lasting disease activity suppression in relapsing-remitting multiple sclerosis (RRMS). The objective of this study was to characterize the immunological reconstitution of T cell subsets and its contribution to the prolonged RRMS suppression following alemtuzumab-induced lymphocyte depletion. The study was performed on blood samples from RRMS patients enrolled in the CARE-MS II clinical trial, which was recently completed and led to the submission of alemtuzumab for U.S. Food and Drug Administration approval as a treatment for RRMS. Alemtuzumab-treated patients exhibited a nearly complete depletion of circulating CD4(+) lymphocytes at day 7. During the immunological reconstitution, CD4(+)CD25(+)CD127(low) regulatory T cells preferentially expanded within the CD4(+) lymphocytes, reaching their peak expansion at month 1. The increase in the percentage of TGF-β1-, IL-10-, and IL-4-producing CD4(+) cells reached a maximum at month 3, whereas a significant decrease in the percentages of Th1 and Th17 cells was detected at months 12 and 24 in comparison with the baseline. A gradual increase in serum IL-7 and IL-4 and a decrease in IL-17A, IL-17F, IL-21, IL-22, and IFN-γ levels were detected following treatment. In vitro studies have demonstrated that IL-7 induced an expansion of CD4(+)CD25(+)CD127(low) regulatory T cells and a decrease in the percentages of Th17 and Th1 cells. In conclusion, our results indicate that differential reconstitution of T cell subsets and selectively delayed CD4(+) T cell repopulation following alemtuzumab-induced lymphopenia may contribute to its long-lasting suppression of disease activity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alemtuzumab
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antigens, CD / immunology*
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Antigens, Neoplasm / immunology*
  • CD52 Antigen
  • Cells, Cultured
  • Clinical Trials, Phase III as Topic
  • Glycoproteins / immunology*
  • Humans
  • Immunologic Memory / drug effects
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Interferon beta-1a
  • Interferon-beta / pharmacology
  • Interferon-beta / therapeutic use
  • Interleukin-7 / pharmacology
  • Lymphocyte Depletion / methods*
  • Lymphokines / blood
  • Lymphokines / metabolism
  • Lymphopenia / blood
  • Lymphopenia / chemically induced
  • Lymphopenia / immunology*
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / immunology
  • Randomized Controlled Trials as Topic
  • T-Lymphocyte Subsets / chemistry
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology*
  • Th1 Cells / pathology
  • Th17 Cells / pathology
  • Time Factors


  • Antibodies, Monoclonal, Humanized
  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • CD52 Antigen
  • CD52 protein, human
  • Glycoproteins
  • Immunosuppressive Agents
  • Interleukin-7
  • Lymphokines
  • Alemtuzumab
  • Interferon-beta
  • Interferon beta-1a