Importance of CD80/CD86–CD28 interactions in the recognition of target cells by CD8+CD122+ regulatory T cells
Importance of CD80/CD86–CD28 interactions in the recognition of target cells by CD8+CD122+ regulatory T cells
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DOI：
10.1111/j.1365-2567.2007.02747.x
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发表时间：
2008-05
期刊：
影响因子：
6.4
通讯作者：
Zhe Shi;M. Rifa’i;Young Ho Lee;H. Shiku;K. Isobe;Haruhiko Suzuki
中科院分区：
文献类型：
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作者：
Zhe Shi;M. Rifa’i;Young Ho Lee;H. Shiku;K. Isobe;Haruhiko Suzuki
CD 8 + CD 122+调节性T细胞是一种新发现的天然调节性T细胞，可产生白细胞介素-10（IL-10）并有效抑制CD 8+和CD 4+靶细胞产生干扰素-γ（IFN-γ）。在这项研究中，负责识别的靶细胞的CD 8 + CD 122+调节性T细胞的分子机制进行了研究，通过使用在体外培养系统，重建这些细胞的调节作用。当CD 8 + CD 122+调节性T细胞单独被固定化抗CD 3抗体刺激时，它们不产生IL-10，并且不抑制同种异体靶T细胞的IFN-γ产生，但是当被抗CD 3加抗CD 28包被珠刺激时，它们明显产生IL-10，并且抑制靶细胞的IFN-γ产生。主要组织相容性复合体I类缺陷T细胞产生的IFN-γ也被抗CD 3加抗CD 28抗体刺激的CD 8 + CD 122+调节性T细胞抑制，但不被单独抗CD 3刺激的细胞抑制。通过在培养物中加入特异性中和抗体，检查在调节细胞或靶细胞上表达的细胞表面分子的阻断的实验表明，CD 80、CD 86和CD 28分子参与调节作用，但细胞毒性T淋巴细胞抗原-4、诱导性共刺激分子（ICOS）和程序性死亡-1（PD-1）分子不参与。最后，从CD 28-敲除（CD 28-/-）小鼠中分离的CD 8 + CD 122+细胞没有显示出调节活性。这些结果表明，CD 8 + CD 122+调节性T细胞通过CD 80/CD 86-CD 28分子的相互作用识别靶T细胞，成为产生抑制因子如IL-10的活性调节细胞。
CD8+CD122+ regulatory T cells are a newly identified, naturally occurring type of regulatory T cell that produce interleukin‐10 (IL‐10) and effectively suppress interferon‐γ (IFN‐γ) production from both CD8+ and CD4+ target cells. Molecular mechanisms responsible for the recognition of target cells by CD8+CD122+ regulatory T cells were investigated in this study by using an in vitro culture system that reconstitutes the regulatory action of these cells. CD8+CD122+ regulatory T cells did not produce IL‐10 and did not suppress the IFN‐γ production of allogeneic target T cells when they were stimulated by immobilized anti‐CD3 antibody alone, but they clearly produced IL‐10 and suppressed the IFN‐γ production of target cells when stimulated by anti‐CD3 plus anti‐CD28‐coated beads. IFN‐γ production by major histocompatibility complex‐class I‐deficient T cells was also suppressed by CD8+CD122+ regulatory T cells stimulated with anti‐CD3 plus anti‐CD28 antibody but was not suppressed by cells stimulated by anti‐CD3 alone. Experiments examining the blockade of cell surface molecules expressed on either the regulatory cells or the target cells by adding specific neutralizing antibodies in the culture indicated that CD80, CD86, and CD28 molecules were involved in the regulatory action, but cytotoxic T lymphocyte antigen‐4, inducible costimulatory molecule (ICOS) and programmed death‐1 (PD‐1) molecules were not. Finally, CD8+CD122+ cells isolated from CD28‐knockout (CD28−/−) mice showed no regulatory activity. These results indicate that CD8+CD122+ regulatory T cells recognize target T cells via the interaction of CD80/CD86–CD28 molecules to become active regulatory cells that produce suppressive factors such as IL‐10.