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


MeSH Major

  • Antigens, CD4
  • Bone Marrow Cells
  • Killer Cells, Natural
  • Receptors, Interleukin-2
  • T-Lymphocytes


  • 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 x C57BL/6) F(1) 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-beta mAb treatment also increased NK cell-mediated BM graft rejection, suggesting that the NK cell suppression is exerted through TGF-beta. 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.

publication date

  • April 4, 2006



  • Academic Article



  • eng

PubMed Central ID

  • PMC1459377

Digital Object Identifier (DOI)

  • 10.1073/pnas.0509249103

PubMed ID

  • 16567639

Additional Document Info

start page

  • 5460

end page

  • 5


  • 103


  • 14