Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3
Tolerance induced by inhaled antigen involves CD4+ T cells expressing membrane-bound TGF-β and FOXP3
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DOI：
10.1172/jc1200420509
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发表时间：
2004-07-01
影响因子：
15.9
通讯作者：
Ray, A
中科院分区：
文献类型：
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作者：
Ostroukhova, M;Seguin-Devaux, C;Ray, A
在正常情况下，呼吸道在面对持续的抗原激发时保持免疫耐受。使用反复暴露于低剂量雾化抗原诱导的耐受性小鼠模型，我们显示了CD 4（+）T细胞在耐受性的建立和维持中的重要贡献。CD 4（+）T细胞表达细胞表面和可溶性TGF-β，并在过继转移到幼稚受体小鼠时抑制过敏表型的发展。虽然在炎症小鼠中可检测到表达细胞表面TGF-β的细胞，尽管与耐受化小鼠相比频率较低，但仅来自耐受化小鼠的细胞表达FOXP 3。在体外和体内阻断TGF-β可干扰免疫抑制。尽管在细胞表面表达TGF-β（TGF-β（+））和不表达TGF-β（-）的细胞分泌相同水平的可溶性TGF-β，但只有前者能够减弱小鼠过敏表型的发展。引人注目的是，将TGF-β（+）细胞与其余细胞分离允许TGF-β（-）细胞响应于抗原而增殖。我们提出了一个抗原诱导的免疫耐受模型，该模型涉及与共表达膜结合TGF-β和FOXP 3的调节性CD 4（+）T细胞的细胞-细胞接触。
Under normal circumstances, the respiratory tract maintains immune tolerance in the face of constant antigen provocation. Using a murine model of tolerance induced by repeated exposure to a low dose of aerosolized antigen, we show an important contribution by CD4(+) T cells in the establishment and maintenance of tolerance. The CD4(+) T cells expressed both cell surface and soluble TGF-beta and inhibited the development of an allergic phenotype when adoptively transferred to naive recipient mice. While cells expressing cell surface TGF-beta were detectable in mice with inflammation, albeit at a lower frequency compared with that in tolerized mice, only those from tolerized mice expressed FOXP3. Blockade of TGF-beta in vitro and in vivo interfered with immunosuppression. Although cells that expressed TGF-beta on the cell surface (TGF-beta(+)), as well as the ones that did not (TGF-beta(-)), secreted equivalent levels of soluble TGF-beta, only the former were able to blunt the development of an allergic phenotype in mice. Strikingly, separation of the TGF-beta(+) cells from the rest of the cells allowed the TGF-beta(-) cells to proliferate in response to, antigen. We propose a model of antigen-induced tolerance that involves cell-cell contact with regulatory CD4(+) T cells that coexpress membrane-bound TGF-beta and FOXP3.