Hoek Aad, Rutten Victor P M G, Kool Jolanda, Arkesteijn Ger J A, Bouwstra Ruth J, Van Rhijn Ildiko, Koets Ad P
Division of Immunology, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL Utrecht, The Netherlands.
Vet Res. 2009 Jan-Feb;40(1):6. doi: 10.1051/vetres:2008044. Epub 2008 Oct 18.
Regulatory T cells (Treg) are regarded essential components for maintenance of immune homeostasis. Especially CD4(+)CD25(high) T cells are considered to be important regulators of immune reactivity. In humans and rodents these natural Treg are characterized by their anergic nature, defined as a non-proliferative state, suppressive function and expression of Foxp3. In this study the potential functional role of flowcytometry-sorted bovine white blood cell populations, including CD4(+)CD25(high) T cells and gammadelta T cell subpopulations, as distinct ex vivo regulatory cells was assessed in co-culture suppression assays. Our findings revealed that despite the existence of a distinct bovine CD4(+)CD25(high) T cell population, which showed Foxp3 transcription/expression, natural regulatory activity did not reside in this cell population. In bovine co-culture suppression assays these cells were neither anergic nor suppressive. Subsequently, the following cell populations were tested functionally for regulatory activity: CD4(+)CD25(low) T cells, WC1(+), WC1.1(+) and WC1.2(+) gammadelta T cells, NK cells, CD8(+) T cells and CD14(+) monocytes. Only the WC1.1(+) and WC1.2(+) gammadelta T cells and CD14(+) monocytes proved to act as regulatory cells in cattle, which was supported by the fact that these regulatory cells showed IL-10 transcription/expression. In conclusion, our data provide first evidence that cattle CD4(+)CD25(high)Foxp3(+) and CD4(+)CD25(low) T cells do not function as Treg ex vivo. The bovine Treg function appears to reside in the gammadelta T cell population, more precisely in the WC1.1(+) and the WC1.2(+) subpopulation, major populations present in blood of cattle in contrast to non-ruminant species.
调节性T细胞（Treg）被认为是维持免疫稳态的重要组成部分。特别是CD4(+)CD25(高) T细胞被认为是免疫反应性的重要调节因子。在人类和啮齿动物中，这些天然Treg的特征在于其无反应性，定义为非增殖状态、抑制功能和Foxp3的表达。在本研究中，通过共培养抑制试验评估了流式细胞术分选的牛白细胞群体，包括CD4(+)CD25(高) T细胞和γδ T细胞亚群作为不同的体外调节细胞的潜在功能作用。我们的研究结果表明，尽管存在一个独特的牛CD4(+)CD25(高) T细胞群体，其显示出Foxp3转录/表达，但天然调节活性并不存在于该细胞群体中。在牛共培养抑制试验中，这些细胞既无反应性也无抑制性。随后，对以下细胞群体进行了调节活性的功能测试：CD4(+)CD25(低) T细胞、WC1(+)、WC1.1(+)和WC1.2(+)γδ T细胞、NK细胞、CD8(+) T细胞和CD14(+)单核细胞。只有WC1.1(+)和WC1.2(+)γδ T细胞以及CD14(+)单核细胞被证明在牛中作为调节细胞发挥作用，这一事实得到了这些调节细胞显示IL-10转录/表达的支持。总之，我们的数据首次证明牛CD4(+)CD25(高)Foxp3(+)和CD4(+)CD25(低) T细胞在体外不作为Treg发挥作用。牛的Treg功能似乎存在于γδ T细胞群体中，更确切地说是在WC1.1(+)和WC1.2(+)亚群中，与非反刍动物物种相比，这是牛血液中的主要群体。
