Nagai Yasuhiro, Aso Hisashi, Ogasawara Hideki, Tanaka Sachi, Taketa Yoshikazu, Watanabe Kouichi, Ohwada Shyuichi, Rose Michael T, Kitazawa Haruki, Yamaguchi Takahiro
Laboratory of Functional Morphology, Tohoku University, Sendai, Japan.
J Immunol. 2008 Nov 1;181(9):6073-81. doi: 10.4049/jimmunol.181.9.6073.
Stem/Progenitor cells in the postnatal pituitary gland are embedded in a marginal cell layer around Rathke's pouch. However, the nature and behavior of anterior pituitary progenitor cells remain unclear. We established bovine anterior pituitary progenitor cell line (BAPC)-1 from the anterior pituitary gland, which expressed stem/progenitor cell-related genes and several inflammatory cytokines. To characterize and localize these pituitary progenitor cells, we produced a mAb (12B mAb) against BAPC-1. The 12B mAb recognized the 4Ig-B7-H3 molecule, which is a costimulatory molecule and negative regulator in T cell activation. WC1(+) gammadelta T cells in young bovine PBMC express the 4Ig-B7-H3 molecule, but few or no 4Ig-B7-H3-immunoreactive cells are expressed in PBMC in adult cattle. The 12B-immunoreactive cells in the bovine anterior pituitary gland were localized around Rathke's pouch and expressed IL-18 and MHC class II. However, the number of 12B-immunoreactive cells was lower in adult than in young cattle. BAPC-1 expressed IL-18 and MHC class II, and demonstrated phagocytotic activity. BAPC-1 also had the ability to promote CD25 expression in PBMC after 5 days of coculture, and blocking 4Ig-B7-H3 x 12B mAb enhanced their expression of CD25. In addition, the 12B-immunoreactive cells were observed around the pars tuberalis closely bordering the median eminence and in the blood vessels of the primary portal plexus in the anterior pituitary gland. These results suggest that an established BAPC-1 may originate from these progenitor cells, and that the progenitor cells with 4Ig-B7-H3 may play a critical role in the immunoendocrine network.
出生后垂体中的干/祖细胞嵌入在拉特克囊周围的边缘细胞层中。然而,垂体前叶祖细胞的性质和行为仍不清楚。我们从垂体前叶建立了牛垂体前叶祖细胞系(BAPC)-1,其表达干/祖细胞相关基因和几种炎性细胞因子。为了表征和定位这些垂体祖细胞,我们制备了一种针对BAPC-1的单克隆抗体(12B单克隆抗体)。12B单克隆抗体识别4Ig-B7-H3分子,该分子是T细胞活化中的共刺激分子和负调节因子。幼年牛外周血单核细胞中的WC1(+)γδT细胞表达4Ig-B7-H3分子,但成年牛外周血单核细胞中很少或不表达4Ig-B7-H3免疫反应性细胞。牛垂体前叶中的12B免疫反应性细胞定位于拉特克囊周围,并表达IL-18和MHC II类分子。然而,成年牛中12B免疫反应性细胞的数量低于幼年牛。BAPC-1表达IL-18和MHC II类分子,并表现出吞噬活性。共培养5天后,BAPC-1还具有促进外周血单核细胞中CD25表达的能力,阻断4Ig-B7-H3×12B单克隆抗体可增强其CD25表达。此外,在紧邻正中隆起的结节部周围以及垂体前叶初级门静脉丛的血管中观察到12B免疫反应性细胞。这些结果表明,已建立的BAPC-1可能起源于这些祖细胞,并且具有4Ig-B7-H3的祖细胞可能在免疫内分泌网络中起关键作用。