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 language | English |
|---|---|
| Pages (from-to) | 5460-5465 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 103 |
| Issue number | 14 |
| DOIs | |
| State | Published - Apr 4 2006 |
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Keywords
- Anti-CD25
- Bone marrow transplantation
- Foxp3
- Hybrid resistance
ASJC Scopus subject areas
- Genetics
- General
Cite this
Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells. / Barao, Isabel; Hanash, Alan M.; Hallett, William; Welniak, Lisbeth A.; Sun, Kai; Redelman, Doug; Blazar, Bruce R.; Levy, Robert B; Murphy, William J.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 14, 04.04.2006, p. 5460-5465.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells
AU - Barao, Isabel
AU - Hanash, Alan M.
AU - Hallett, William
AU - Welniak, Lisbeth A.
AU - Sun, Kai
AU - Redelman, Doug
AU - Blazar, Bruce R.
AU - Levy, Robert B
AU - Murphy, William J.
PY - 2006/4/4
Y1 - 2006/4/4
N2 - 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.
AB - 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.
KW - Anti-CD25
KW - Bone marrow transplantation
KW - Foxp3
KW - Hybrid resistance
UR - http://www.scopus.com/inward/record.url?scp=33645759979&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645759979&partnerID=8YFLogxK
U2 - 10.1073/pnas.0509249103
DO - 10.1073/pnas.0509249103
M3 - Article
VL - 103
SP - 5460
EP - 5465
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 14
ER -