期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 35, 期 9, 页码 2598-2607出版社
WILEY
DOI: 10.1002/eji.200526077
关键词
Foxp3; regulatory T cells; GVHD; transplantation
类别
资金
- NCI NIH HHS [CA 84132, CA 18029] Funding Source: Medline
- NIAID NIH HHS [AI 51693] Funding Source: Medline
- NIDDK NIH HHS [DK56465] Funding Source: Medline
Adoptive transfer of polyclonal CD4(+)CD25(+) regulatory T cells (Treg) can tolerize transplantation alloresponses. Treg are activated via their specific TCR, but the antigen specificity of wild-type Treg remains elusive, and therefore controlling potency and duration of Treg activity in the transplantation setting is still not feasible. In this study, we used murine graft-versus-host disease (GVHD) as a model system to show that antigen-specific Treg suppress the response of T effector cells to alloantigens in vitro and prevent GVHD in vivo. The suppressive potential of antigen-specific Treg was much greater than that of polyclonal Treg. To acquire large numbers of antigen-specific Treg, we transduced CD4(+)CD25(-) cells with foxp3, and found that these foxp3-induced Treg suppress alloresponses in vitro and prevent GVHD in vivo as effectively as naturally derived CD4(+)CD25(+) Treg. Furthermore, we used an antigen-specific CD4 Th1 clone as a source of foxp3-induced Treg after transduction with foxp3, and found those Treg to effectively prevent GVHD in an antigen-dependent manner. The findings of this study provide a basis for the concept that the onset and potency of the suppression by Treg can be regulated, and suggest a novel approach to enhance the feasibility and effectiveness of inducing tolerance by Treg as an adoptive immunotherapy in transplantation.
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