CD49d provides access to 'untouched' human Foxp3+ Treg free of contaminating effector cells

Markus Kleinewietfeld, Mireille Starke, Diletta Di Mitri, Giovanna Borsellino, Luca Battistini, Olaf Rötzschke, Kirsten Falk

Research output: Contribution to journalArticlepeer-review

Abstract

The adoptive transfer of regulatory Foxp3 + T (Treg) cells has been shown in various animal models to prevent inflam- matory immune and autoimmune dis- eases. Translation into therapeutic appli- cations, however, is hindered by the lack of suitable techniques and markers. CD25, commonly used to isolate Treg cells from mice, has only limited value in humans as it is also present on proinflammatory CD4 + effector cells. Here we show that clean populations of human Foxp3 + Treg cells can be obtained with antibodies directed against CD49d. The marker is present on proinflammatory peripheral blood mononuclear cells but is absent on immune-suppressive Treg cells. Depletion with a-CD49d removes contaminating inter- feron-? (IFN-?)- and interleukin-17 (IL-17)- secreting cells from Treg preparations of CD4 +CD25 high cells. More importantly, in combination with a-CD127 it allows the iso- lation of "untouched" Foxp3 + Treg (ie, cells that have not been targeted by an antibody during purification). The removal of CD49d +/ CD127 + cells leaves a population of Foxp3 + Treg virtually free of contaminating CD25 + effector cells. The cells can be expanded in vitro and are effective suppressors both in vitro and in vivo. Thus, CD49d provides access to highly pure populations of un- touched Foxp3 + Treg cells conferring maxi- mal safety for future clinical applications.

Original languageEnglish
Pages (from-to)827-836
Number of pages10
JournalBlood
Volume113
Issue number4
DOIs
Publication statusPublished - Jan 22 2009

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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