Subpopulations of bovine WC1+ γδ T cells rather than CD4+CD25highFoxp3+ T cells act as immune regulatory cells ex vivo
Subpopulations of bovine WC1+ γδ T cells rather than CD4+CD25highFoxp3+ T cells act as immune regulatory cells ex vivo
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DOI：
10.1051/vetres:2008044
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
Koets, Ad P.
中科院分区：
文献类型：
--
作者：
Hoek, Aad;Rutten, Victor P. M. G.;Koets, Ad P.
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CD 4（+）CD 25（高）T细胞被认为是免疫反应性的重要调节剂。在人类和啮齿动物中，这些天然Treg的特征在于其无反应性性质，定义为非增殖状态、抑制功能和Foxp 3的表达。在本研究中，在共培养抑制试验中评估了流式细胞术分选的牛白色血细胞群（包括CD 4（+）CD 25（高）T细胞和γ δ T细胞亚群）作为不同离体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CD 4（+）CD 25（高）T细胞群，其中显示Foxp 3转录/表达，自然调节活性并不存在于这个细胞群。在牛共培养抑制试验中，这些细胞既不无反应性也不具有抑制性。随后，对以下细胞群的调节活性进行功能性检测：CD 4（+）CD 25（低）T细胞、WC 1（+）、WC 1.1（+）和WC 1.2（+）γ δ T细胞、NK细胞、CD 8（+）T细胞和CD 14（+）单核细胞。只有WC1.1（+）和WC1.2（+）γ δ T细胞和CD 14（+）单核细胞被证明是牛的调节细胞，这得到了这些调节细胞显示IL-10转录/表达的事实的支持。总之，我们的数据提供了牛CD 4（+）CD 25（高）Foxp 3（+）和CD 4（+）CD 25（低）T细胞体外不起Treg作用的第一个证据。牛Treg功能似乎存在于γ δ T细胞群中，更确切地说存在于WC1.1（+）和WC1.2（+）亚群中，与非反刍动物物种相比，这些亚群是牛血液中存在的主要群体。
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 gamma delta 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(+) gamma delta T cells, NK cells, CD8(+) T cells and CD14(+) monocytes. Only the WC1.1(+) and WC1.2(+) gamma delta 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 gamma delta 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.