Kawamura H, Kawamura T, Kokai Y, Mori M, Matsuura A, Oya H, Honda S, Suzuki S, Weerashinghe A, Watanabe H, Abo T
Department of Immunology, Niigata University School of Medicine, Niigata, Japan; and Department of Pathology, Sapporo Medical University, Sapporo, Japan.
J Immunol. 1999 May 15;162(10):5957-64.
When we attempted to characterize the immunological state in G-CSF transgenic mice, a large number of not only granulocytes but also lymphoid cells expanded in various immune organs. Such lymphoid cells were present at unusual sites of these organs, e.g., the parenchymal space in the liver. We then determined the phenotype of these lymphoid cells by immunofluorescence tests. It was demonstrated that CD3intIL-2Rbeta+ cells (i.e., extrathymic T cells), including the NK1.1+ subset of CD3int cells (i.e., NKT cells), increased in the liver and all other tested organs. These T cells as well as NK cells mediated NK and NK-like cytotoxicity, especially at youth. However, they were not able to mediate such cytotoxicity in the presence of granulocytes. This result might be associated with deficiency in the hybrid resistance previously ascribed to these mice. In other words, G-CSF transgenic mice had a large number of extrathymic T cells (including NKT cells) and NK cells that mediate hybrid resistance, but their function was suppressed by activated granulocytes. Indeed, these granulocytes showed an elevated level of Ca2+ influx upon stimulation. The present results suggest that, in parallel with overactivation of granulocytes, extrathymic T cells and NK cells are concomitantly activated in number but that their function is suppressed in G-CSF transgenic mice.
当我们试图描述粒细胞集落刺激因子（G-CSF）转基因小鼠的免疫状态时，不仅大量粒细胞，而且多种免疫器官中的淋巴细胞都出现了扩增。这些淋巴细胞存在于这些器官的异常部位，例如肝脏的实质间隙。然后，我们通过免疫荧光试验确定了这些淋巴细胞的表型。结果表明，肝脏及所有其他检测器官中，CD3intIL-2Rbeta+细胞（即胸腺外T细胞），包括CD3int细胞的NK1.1+亚群（即自然杀伤T细胞，NKT细胞）数量增加。这些T细胞以及自然杀伤细胞介导自然杀伤和自然杀伤样细胞毒性，尤其是在幼年时。然而，在存在粒细胞的情况下，它们无法介导这种细胞毒性。这一结果可能与先前归因于这些小鼠的混合抗性缺陷有关。换句话说，G-CSF转基因小鼠有大量介导混合抗性的胸腺外T细胞（包括NKT细胞）和自然杀伤细胞，但它们的功能受到活化粒细胞的抑制。事实上，这些粒细胞在受到刺激后钙离子内流水平升高。目前的结果表明，与粒细胞的过度活化同时，胸腺外T细胞和自然杀伤细胞在数量上也随之被激活，但在G-CSF转基因小鼠中它们的功能受到抑制。
