Induction of tolerance by adoptive transfer of Treg cells.
Naturally arising CD4+CD25+ regulatory T (Treg) cells can be exploited to establish immunologic tolerance to allogeneic transplants. In vivo exposure of CD4+CD25+ T cells from normal naive mice to alloantigen in a T cell-deficient environment elicits spontaneous expansion of alloantigen-specific CD4+CD25+ natural Treg cells, which are able to suppress allograft rejection mediated by subsequently transferred naive T cells, leading to long-term graft tolerance. Similar antigen-specific expansion of natural Treg cells can also be achieved in vitro by stimulating CD4+CD25+ T cells from normal animals with alloantigen in the presence of high doses of interleukin-2. The expanded CD4+CD25+ Treg cells are even capable of suppressing secondary mixed leukocyte reaction in vitro and, by in vivo transfer, establishing antigen-specific long-term graft tolerance. Thus, in vivo or in vitro, direct or indirect ways of alloantigen-specific expansion of naturally arising CD4+CD25+ Treg cells can establish antigen-specific dominant tolerance to allogeneic transplants.
Nagahama
Kanji
K
Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Nishimura
Eiji
E
Sakaguchi
Shimon
S
D019264:Adoptive Transfer / Q000379:methods*; D000818:Animals; D016038:Skin Transplantation / Q000276:immunology / Q000379:methods; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000637:transplantation*; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous