γδ T cells regulate mucosally induced tolerance in a dose-dependent fashion
γδ T cells regulate mucosally induced tolerance in a dose-dependent fashion
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DOI：
10.1093/intimm/11.12.1907
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发表时间：
1999-12-01
影响因子：
4.4
通讯作者：
Kiyono, H
中科院分区：
文献类型：
--
作者：
Fujihashi, K;Dohi, T;Kiyono, H
我们使用γ δ TCR缺陷（TCR δ（-/-））小鼠来检查γ δ T细胞在诱导粘膜应答和对高剂量与低剂量口服抗原的全身耐受性中的作用。当TCR δ（-/-）或TCR δ（+/+）小鼠在胃肠外攻击之前用高剂量卵清蛋白（OVA）口服免疫时，两种类型小鼠的全身IgG和IgE抗体应答均显著降低，而粘膜伊加应答仅在TCR δ（-/-）小鼠中降低。高剂量OVA、抗原诱导的T（h）1和T（h）2可降低TCR δ（-/-）和TCR δ（+/+）小鼠的T细胞增殖反应和迟发型超敏反应，口服耐受的TCR δ（-/-）和TCR δ（+/+）小鼠脾CD 4（+）T细胞的细胞因子产生受到严重抑制。相反，虽然低剂量的OVA在TCR δ（+/+）小鼠中诱导了与IL-10合成水平增加相关的口服耐受性，但TCR δ（-/-）小鼠没有耐受性并且不能产生IL-10。我们的发现表明γ δ T细胞在IL-10介导的低剂量口服耐受性诱导中起重要的免疫调节作用，但不是诱导对以较大剂量给予的口服引入的抗原的全身耐受性的必要参与者。
We used gamma delta TCR-deficient (TCR delta(-/-)) mice to examine the role of gamma delta T cells for induction of mucosal responses and systemic tolerance to high versus low doses of oral antigen. When either TCR delta(-/-) or TCR delta(+/+) mice were immunized orally with a high dose of ovalbumin (OVA) prior to parenteral challenge, systemic IgG and IgE antibody responses were markedly reduced in both types of mice, while mucosal IgA responses were reduced only in the TCR delta(-/-) mice. Reduced T cell proliferative responses and delayed-type hypersensitivity were seen in TCR delta(-/-) and TCR delta(+/+) mice given the high dose of OVA, Antigen-induced T(h)1 and T(h)2,cytokine production by splenic CD4(+) T cells was severely inhibited in orally tolerized TCR delta(-/-) and TCR delta(+/+) mice. In contrast, while oral tolerance associated with increased levels of IL-10 synthesis was induced by a low dose of OVA in TCR delta(+/+) mice, the TCR delta(-/-) mice were not tolerized and failed to produce IL-10, Our findings indicate that gamma delta T cells play a significant immunoregulatory role in IL-10-mediated, low-dose oral tolerance induction, but are not essential participants in the induction of systemic tolerance to orally introduced antigens given in larger doses.