Role of CD4+ regulatory T cells in hyperbaric oxygen-mediated immune nonresponsiveness
Role of CD4+ regulatory T cells in hyperbaric oxygen-mediated immune nonresponsiveness
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DOI：
10.1016/s0198-8859(00)00214-7
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发表时间：
2000-12-01
期刊：
影响因子：
2.7
通讯作者：
Hullett, DA
中科院分区：
文献类型：
--
作者：
MacKenzie, DA;Sollinger, HW;Hullett, DA
我们之前已经证明，高压氧培养（HOC [95% O-2、5% CO2、25 psi]）是一种有效的移植前组织修饰技术，可在小鼠模型中实现同种异体移植物的长期存活并诱导全身免疫耐受。在这里，我们使用体外混合淋巴细胞反应（MLR）来探讨 HOC 处理人类免疫反应的免疫调节作用。用 HOC 预处理同种异体刺激细胞会导致 7 天 MLR 中细胞毒性 T 淋巴细胞 (CTL) 活性、增殖反应和 IFN γ 产生消失。这些反应可以通过在第 0 天添加 IFN γ 或 IL-2 或通过阻断 IL-4 和 IL-10 的活性来恢复。第 4 天添加 IL-2 也不会恢复同种异体特异性 CTL 活性。 HOC处理的细胞未能诱导同种异体特异性CTL并不是由于无反应性的诱导，这一点可以通过在IL-2存在下用同种异体细胞再刺激后未能恢复反应来证明。在再刺激之前去除CD4(+)细胞，可以恢复用HOC处理的同种异体细胞再刺激的MLR培养物中的CTL活性。这些结果表明，chat HOC 诱导的免疫无反应是由 Th2 型环境中 CD4(+) 调节细胞的发育介导的。 (C) 美国组织相容性和免疫遗传学学会，2000 年。由 Elsevier Science Inc. 出版。
We have previously shown that hyperbaric oxygen culture (HOC [95% O-2, 5% CO2, 25 psi]) is an effective pretransplant tissue-modification technique that results in long-term allograft survival and the induction of systemic immune tolerance in a murine model. Here we address the immune modulatory effects of HOC-treatment of human immune responses using the in vitro mixed lymphocyte: reaction (MLR). Pretreatment of allogeneic stimulator cells with HOC results in abrogation of cytotoxic T lymphocyte (CTL) activity, proliferative responses, and IFN gamma production in a 7-day MLR. These responses can be restored either by the addition of IFN gamma or IL-2 on day 0, or by blocking the activity of IL-4 and IL-10. The addition of IL-2 on day 4 does nor restore allospecific CTL activity. The failure of HOC-treated cells to induce allospecific CTL is not due to the induction of anergy, demonstrated by the failure to restore responses after restimulation with allogeneic cells in the presence of IL-2. Removal of CD4(+) cells prior to restimulation, results in restoration of CTL activity in MLR cultures restimulated with HOC-treated allogeneic cells. These results suggest chat HOC-induced immune nonresponsiveness is mediated by the development of CD4(+) regulatory cells in a Th2-type environment. (C) American Society for Histocompatibility and Immunogenetics, 2000. Published by Elsevier Science Inc.