Repopulation of blood lymphocyte sub-populations in rheumatoid arthritis patients treated with the depleting humanized monoclonal antibody, CAMPATH-1H

Immunology. 1996 May;88(1):13-9. doi: 10.1046/j.1365-2567.1996.d01-650.x.


Patients with severe rheumatoid arthritis who had failed treatment with conventional therapies were treated with a course of five or 10 daily intravenous infusions of CAMPATH-1H, a humanized antibody against the CD52 antigen, resulting in profound depletion of peripheral blood mononuclear cells. During the subsequent 18 months, lymphocytes were analysed for sub-populations by fluorescence-activated cell sorter (FACS) and for proliferation in response to polyclonal T-cell stimulation with anti-CD3 or staphylococcal enterotoxin B (SEB). Treatment resulted in almost complete depletion of lymphocytes from the blood followed by gradual repopulation. CD16+ natural killer (NK) cells and CD14+ monocytes returned to pretreatment levels within 1-2 months. CD19+ B cells returned to within 50% of pre-treatment levels by day 66 and to within normal range by day 150, whereas CD8+ T cells recovered to 50% of pretreatment levels by day 66, but did not show any further increase during the rest of the study period. The most profound effects were on the CD4+ T lymphocyte sub-population, as the mean CD4+ count did not increase above 20% of pre-treatment level at any time during the study period (550 days), at all the doses tested. The T cells which initially repopulated the blood 1-2 months after treatment, nearly all expressed the activation markers human leucocyte antigen (HLA)-DR and CD45RO, although the percentage of T cells expressing these molecules gradually declined to normal levels over time. Proliferative responses to polyclonal T-cell stimulation (anti-CD3 and SEB) were also significantly reduced in the first few months after treatment, but recovered to pre-treatment levels by day 250. The relationship between these observations and the clinical response is discussed.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD / immunology
  • Antigens, CD / pharmacology*
  • Antigens, Neoplasm*
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / therapy*
  • B-Lymphocytes / immunology
  • CD52 Antigen
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Flow Cytometry
  • Glycoproteins*
  • HLA-DR Antigens / immunology
  • Humans
  • Killer Cells, Natural / immunology
  • Leukocyte Common Antigens / immunology
  • Leukocyte Count
  • Lymphocyte Activation
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / physiology*
  • Male
  • Middle Aged
  • Monocytes / immunology
  • Time Factors


  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Neoplasm
  • CD52 Antigen
  • CD52 protein, human
  • Glycoproteins
  • HLA-DR Antigens
  • Leukocyte Common Antigens