Department of Pathology, The Ohio State University Medical Center, Columbus, OH 43210, USA.
J Immunol. 2013 Mar 1;190(5):2229-40. doi: 10.4049/jimmunol.1201170. Epub 2013 Jan 21.
CXCR3, expressed mainly on activated T and NK cells, is implicated in a host of immunological conditions and can contribute either to disease resolution or pathology. We report the generation and characterization of a novel CXCR3 internal ribosome entry site bicistronic enhanced GFP reporter (CIBER) mouse in which enhanced GFP expression correlates with surface levels of CXCR3. Using CIBER mice, we identified two distinct populations of innate CD8(+) T cells based on constitutive expression of CXCR3. We demonstrate that CXCR3(+) innate CD8(+) T cells preferentially express higher levels of Ly6C and CD122, but lower levels of CCR9 compared with CXCR3(-) innate CD8(+) T cells. Furthermore, we show that CXCR3(+) innate CD8(+) T cells express higher transcript levels of antiapoptotic but lower levels of proapoptotic factors, respond more robustly to IL-2 and IL-15, and produce significantly more IFN-γ and granzyme B. Interestingly, CXCR3(+) innate CD8(+) T cells do not respond to IL-12 or IL-18 alone, but produce significant amounts of IFN-γ on stimulation with a combination of these cytokines. Taken together, these findings demonstrate that CXCR3(+) and CXCR3(-) innate CD8(+) T cells are phenotypically and functionally distinct. These newly generated CIBER mice provide a novel tool for studying the role of CXCR3 and CXCR3-expressing cells in vivo.
CXCR3 主要表达于活化的 T 细胞和自然杀伤（NK）细胞上，与多种免疫状态相关，既能促进疾病缓解，也能导致疾病进展。我们报告了一种新型 CXCR3 内部核糖体进入位点双顺反子增强型绿色荧光蛋白报告（CIBER）小鼠的生成和鉴定，该小鼠中增强型绿色荧光蛋白的表达与 CXCR3 的表面水平相关。利用 CIBER 小鼠，我们根据 CXCR3 的组成型表达，鉴定出了固有 CD8+T 细胞的两个不同亚群。我们证明，与 CXCR3(-)固有 CD8+T 细胞相比，CXCR3(+)固有 CD8+T 细胞优先表达更高水平的 Ly6C 和 CD122，但表达更低水平的 CCR9。此外，我们发现，与 CXCR3(-)固有 CD8+T 细胞相比，CXCR3(+)固有 CD8+T 细胞表达更高水平的抗凋亡因子，但表达更低水平的促凋亡因子，对 IL-2 和 IL-15 反应更强烈，并产生显著更多的 IFN-γ和颗粒酶 B。有趣的是，CXCR3(+)固有 CD8+T 细胞本身对 IL-12 或 IL-18 无反应，但在受到这些细胞因子组合刺激时，能产生大量 IFN-γ。综上，这些发现表明，CXCR3(+)和 CXCR3(-)固有 CD8+T 细胞在表型和功能上存在差异。这些新生成的 CIBER 小鼠为研究 CXCR3 和 CXCR3 表达细胞在体内的作用提供了一种新工具。
