Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis

Bibiana Bielekova, Marta Catalfamo, Susan Reichert-Scrivner, Amy Packer, Magdalena Cerna, Thomas A. Waldmann, Henry McFarland, Pierre A. Henkart, Roland Martin

Research output: Contribution to journalArticle

Abstract

Administration of daclizumab, a humanized mAb directed against the IL-2Rα chain, strongly reduces brain inflammation in multiple sclerosis patients. Here we show that daclizumab treatment leads to only a mild functional blockade of CD4+ T cells, the major candidate in multiple sclerosis pathogenesis. Instead, daclizumab therapy was associated with a gradual decline in circulating CD4+ and CD8+ T cells and significant expansion of CD56bright natural killer (NK) cells in vivo, and this effect correlated highly with the treatment response. In vitro studies showed that NK cells inhibited T cell survival in activated peripheral blood mononuclear cell cultures by a contact-dependent mechanism. Positive correlations between expansion of CD56bright NK cells and contraction of CD4+ and CD8+ T cell numbers in individual patients in vivo provides supporting evidence for NK cell-mediated negative immunoregulation of activated T cells during daclizumab therapy. Our data support the existence of an immunoregulatory pathway wherein activated CD56 bright NK cells inhibit T cell survival. This immunoregulation has potential importance for the treatment of autoimmune diseases and transplant rejection and toward modification of tumor immunity.

Original languageEnglish (US)
Pages (from-to)5941-5946
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number15
DOIs
StatePublished - Apr 11 2006
Externally publishedYes

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Natural Killer Cells
Multiple Sclerosis
T-Lymphocytes
Cell Survival
Therapeutics
Graft Rejection
Encephalitis
Autoimmune Diseases
daclizumab
Immunity
Blood Cells
Cell Culture Techniques
Cell Count
Neoplasms

Keywords

  • CD25
  • IL-2
  • Immunoregulatory natural killer cells

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis. / Bielekova, Bibiana; Catalfamo, Marta; Reichert-Scrivner, Susan; Packer, Amy; Cerna, Magdalena; Waldmann, Thomas A.; McFarland, Henry; Henkart, Pierre A.; Martin, Roland.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 15, 11.04.2006, p. 5941-5946.

Research output: Contribution to journalArticle

Bielekova, Bibiana ; Catalfamo, Marta ; Reichert-Scrivner, Susan ; Packer, Amy ; Cerna, Magdalena ; Waldmann, Thomas A. ; McFarland, Henry ; Henkart, Pierre A. ; Martin, Roland. / Regulatory CD56bright natural killer cells mediate immunomodulatory effects of IL-2Rα-targeted therapy (daclizumab) in multiple sclerosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 15. pp. 5941-5946.
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