Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells

Isabel Barao, Alan M. Hanash, William Hallett, Lisbeth A. Welniak, Kai Sun, Doug Redelman, Bruce R. Blazar, Robert B. Levy, William J. Murphy

Research output: Contribution to journalArticle

112 Scopus citations

Abstract

Naturally occurring CD4+CD25+ T regulatory (Treg) cells have been shown to inhibit adaptive responses by T cells. Natural killer (NK) cells represent an important component of innate immunity in both cancer and infectious disease states. We investigated whether CD4+CD25 + Treg cells could affect NK cell function in vivo by using allogeneic (full H2-disparate) bone marrow (BM) transplantation and the model of hybrid resistance, in which parental marrow grafts are rejected solely by the NK cells of irradiated (BALB/c × C57BL/6) F1 recipients. We demonstrate that the prior removal of host Treg cells, but not CD8+ T cells, significantly enhanced NK cell-mediated BM rejection in both models. The inhibitory role of Treg cells on NK cells was confirmed in vivo with adoptive transfer studies in which transferred CD4+CD25+ cells could abrogate NK cell-mediated hybrid resistance. Anti-TGF-β mAb treatment also increased NK cell-mediated BM graft rejection, suggesting that the NK cell suppression is exerted through TGF-β. Thus, CD4+CD25 + Treg cells can potently inhibit NK cell function in vivo, and their depletion may have therapeutic ramifications for NK cell function in BM transplantation and cancer therapy.

Original languageEnglish (US)
Pages (from-to)5460-5465
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number14
DOIs
StatePublished - Apr 4 2006

Keywords

  • Anti-CD25
  • Bone marrow transplantation
  • Foxp3
  • Hybrid resistance

ASJC Scopus subject areas

  • Genetics
  • General

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