title: Increased B cell and cytotoxic NK cell proportions and increased T cell responsiveness in blood of natalizumab-treated multiple sclerosis patients.
abstract: BACKGROUND
  Changes in the blood lymphocyte composition probably both mediate and reflect the effects of natalizumab treatment in multiple sclerosis, with implications for treatment benefits and risks.
  
  
  METHODS
  A broad panel of markers for lymphocyte populations, including states of activation and co-stimulation, as well as functional T cell responses to recall antigens and mitogens, were assessed by flow cytometry in 40 patients with relapsing multiple sclerosis before and after one-year natalizumab treatment.
  
  
  RESULTS
  Absolute numbers of all major lymphocyte populations increased after treatment, most markedly for NK and B cells. The fraction of both memory and presumed regulatory B cell subsets increased, as did CD3(-)CD56(dim) cytotoxic NK cells, whereas CD3(-)CD56(bright) regulatory NK cells decreased. The increase in cell numbers was further associated with a restored T cell responsiveness to recall antigens and mitogens in functional assays.
  
  
  CONCLUSIONS
  Our data confirms that natalizumab treatment increases the number of lymphocytes in blood, likely mirroring the expression of VLA-4 being highest on NK and B cells. This finding supports reduction of lymphocyte extravasation as a main mode of action, although the differential effects on subpopulation composition suggests that cell-signalling may also be affected. The systemic increase in T cell responsiveness reflects the increase in numbers, and while augmenting anti-infectious responses systemically, localized responses may become correspondingly decreased.
authors: Neurology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, and Department of Neurology, County Council of Östergötland, Linköping, Sweden.
authors: Johan
authors: J
authors: Mellergård
authors: Måns
authors: M
authors: Edström
authors: Maria C
authors: MC
authors: Jenmalm
authors: Charlotte
authors: C
authors: Dahle
authors: Magnus
authors: M
authors: Vrethem
authors: Jan
authors: J
authors: Ernerudh
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002452:Cell Count; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008137:Longitudinal Studies; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000134:cerebrospinal fluid / Q000188:drug therapy* / Q000276:immunology; D000069442:Natalizumab; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab