Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells
Suppression of natural killer cell-mediated bone marrow cell rejection by CD4+CD25+ regulatory T cells
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DOI：
10.1073/pnas.0509249103
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发表时间：
2006-04-04
影响因子：
11.1
通讯作者：
Murphy, WJ
中科院分区：
文献类型：
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作者：
Barao, I;Hanash, AM;Murphy, WJ
天然存在的CD 4（+）CD 25（+）T调节（Treg）细胞已显示抑制T细胞的适应性应答。自然杀伤（NK）细胞是癌症和传染病状态下先天免疫的重要组成部分。我们通过使用同种异体（完全H2-相异）骨髓（BM）移植和杂交抗性模型研究了CD 4（+）CD 25（+）Treg细胞是否可以影响体内NK细胞功能，在该模型中，亲本骨髓移植物仅被辐射（BALB/c x C57 BL/6）F-1受体的NK细胞排斥。我们证明，在两种模型中，预先去除宿主Treg细胞而不是CD 8（+）T细胞显著增强了NK细胞介导的BM排斥反应。Treg细胞对NK细胞的抑制作用在体内通过过继转移研究得到证实，其中转移的CD 4（+）CD 25（+）细胞可以消除NK细胞介导的杂交抗性。抗TGF-β mAb治疗也增加了NK细胞介导的BM移植物排斥，表明NK细胞抑制是通过TGF-β发挥作用的。因此，CD 4（+）CD 25（+）Treg细胞可以在体内有效地抑制NK细胞功能，并且它们的消耗可能对BM移植和癌症治疗中的NK细胞功能具有治疗性分支。
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.