The suppression of delayed-type hypersensitivity by CD8+ regulatory T cells requires interferon-γ
The suppression of delayed-type hypersensitivity by CD8+ regulatory T cells requires interferon-γ
复制标题
DOI：
10.1111/j.1365-2567.2006.02486.x
复制
发表时间：
2007-01-01
期刊：
影响因子：
6.4
通讯作者：
Vella, Anthony T.
中科院分区：
文献类型：
--
作者：
Cone, Robert E.;Li, Xingya;Vella, Anthony T.
CD8(+) 调节（抑制）T 细胞是由小鼠脾脏中复杂的细胞途径诱导产生的，这些小鼠的前房 (AC) 是一个免疫豁免部位，注射了抗原。尽管这些CD8+调节性T细胞对自身和非自身抗原的免疫反应执行抗原特异性调节功能，但这些调节细胞的激活或功能机制尚不清楚。在这里，我们描述了一种通过将抗原注射到 AC 中诱导脾 CD8+ 调节性 T 细胞激活的新机制。用三硝基苯和牛血清白蛋白 (TNP-BSA) 免疫小鼠可扩增 AC 诱导的脾 CD8(+) 调节性 T 细胞，当转移至免疫的、受到攻击的小鼠时，抑制接触敏感性的启动。这些CD8(+)调节性T细胞的产生独立于穿孔素，表明它们不是典型的细胞毒性T细胞。 Fas配体（FasL）缺陷的CD8（+）调节性T细胞功能通过加入外源性干扰素-γ（IFN-γ）得以挽救，这表明CD8（+）调节性T细胞表达FasL是可有可无的，但IFN-γ则不然。最终，我们证明这些CD8+调节性T细胞的产生独立于IFN-γ，但它们的抑制功能需要IFN-γ受体刺激。
CD8(+) regulatory (suppressor) T cells are induced by complex cellular pathways in the spleens of mice that have received an injection of antigen into the anterior chamber (AC) of an eye, an immune-privileged site. Although these CD8(+) regulatory T cells perform an antigen-specific regulatory function for an immune response to self and non-self antigens, the mechanisms of the activation or function of these regulatory cells are not clear. Here, we describe a novel mechanism for the activation of splenic CD8(+) regulatory T cells induced by injection of antigen into the AC. Immunization of mice with trinitrophenyl and bovine serum albumin (TNP-BSA) amplified AC-induced splenic CD8(+) regulatory T cells that suppressed the initiation of contact sensitivity when transferred to immunized, challenged mice. These CD8(+) regulatory T cells were produced independently of perforin, indicating that they are not canonical cytotoxic T cells. Fas ligand (FasL)-deficient CD8(+) regulatory T-cell function was rescued by inclusion of exogenous interferon-gamma (IFN-gamma), demonstrating that the expression of FasL by CD8(+) regulatory T cells was dispensable, but IFN-gamma was not. Ultimately, we demonstrated that the generation of these CD8(+) regulatory T cells occurred independently of IFN-gamma, but their suppressor function required IFN-gamma receptor stimulation.