Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis

Eur J Immunol. 2005 Nov;35(11):3332-42. doi: 10.1002/eji.200535075.


Following lymphocyte depletion, homeostatic mechanisms drive the reconstitution of lymphocytes. We prospectively studied this process in 16 patients for 1 year after a single pulse of treatment with Campath-1H, a humanised anti-CD52 monoclonal antibody. We observed two phases of lymphocyte reconstitution. In the first 6 months after treatment the precursor frequency and proliferation index of the patients' autologous mixed lymphocyte reaction increased; the depleted T cell pool was dominated by memory T cells, especially (CD4+)CD25high T cells, a putative regulatory phenotype; and there was a non-significant rise in peripheral mononuclear cell FoxP3 mRNA expression and fall in constitutive cytokine mRNA expression. In the later phase, from 6-to-12 months after Campath-1H, these changes reversed and there was a rise in ROG mRNA expression. However, total CD4+ numbers remained below 50% of pre-treatment levels at 12 months, perhaps reflecting a failure in homeostasis. This was not due to an impaired IL-7 response, as in rheumatoid arthritis, nor to a lack of IL-7 receptors, which are found on fewer human (CD4+)CD25high than naive cells. We speculate that CCL21 and IL-15 responses to lymphopaenia may be suboptimal in multiple sclerosis.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alemtuzumab
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Chemokine CCL21
  • Chemokines, CC / blood
  • Female
  • Gene Expression Regulation / immunology
  • Homeostasis / genetics
  • Homeostasis / immunology*
  • Humans
  • Immunologic Memory / genetics
  • Interleukin-15 / blood
  • Interleukin-7 / blood
  • Lymphocyte Depletion*
  • Male
  • Middle Aged
  • Multiple Sclerosis / immunology*
  • Multiple Sclerosis / therapy*
  • Prospective Studies
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Interleukin-7 / biosynthesis
  • Receptors, Interleukin-7 / genetics
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neoplasm
  • CCL21 protein, human
  • Chemokine CCL21
  • Chemokines, CC
  • Interleukin-15
  • Interleukin-7
  • Receptors, Interleukin-2
  • Receptors, Interleukin-7
  • Alemtuzumab