Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
J Immunol. 2013 Feb 15;190(4):1758-66. doi: 10.4049/jimmunol.1202567. Epub 2013 Jan 14.
Mast cells (MC) and basophils share expression of the high-affinity receptor for IgE (FcεRI) but can be distinguished by their divergent expression of KIT and CD49b. In BALB/c mice, MC lineage cells expressing high levels of FcεRI by flow cytometry were seen only in bone marrow whereas those expressing intermediate levels of FcεRI were present in bone marrow and spleen of naive mice and in mesenteric lymph nodes (mLN) of Trichinella spiralis-infected mice. These FcεRI(+)KIT(+)CD49b(-) cells had a membrane phenotype similar to i.p. connective tissue-type MC, but were smaller and hypogranular by flow cytometry forward and side scatter profiles, respectively. Consistent with this, they lacked the prominent secretory granules identified by histochemistry and immunodetection for the MC-specific granule proteases that are readily seen in mature jejunal mucosal MC that also are induced by the infection and present at the same time. The concentration of these MC lineage cells in mLN determined by flow cytometry was comparable to that of MC progenitors (MCp) measured by limiting dilution and clonal expansion with maturation. We observed upregulation of IL-4 transcription by MCp in mLN and spleens of helminth-infected 4get mice, and we demonstrated by intracellular cytokine staining production of IL-4 and IL-6 by the mLN MCp in helminth-infected mice. Furthermore, treatment of helminth-infected mice with anti-FcεRI mAb, a protocol known to deplete basophils, also depleted mLN MCp. Thus, this study identifies a hypogranular subset of MCp recruited to mLN by helminth infection that may be an important unrecognized source of cytokines.
肥大细胞 (MC) 和嗜碱性粒细胞都表达高亲和力 IgE 受体 (FcεRI),但可以通过其 KIT 和 CD49b 的不同表达来区分。在 BALB/c 小鼠中,通过流式细胞术观察到骨髓中表达高水平 FcεRI 的 MC 谱系细胞,而在幼稚小鼠的骨髓和脾脏以及旋毛虫感染小鼠的肠系膜淋巴结 (mLN) 中存在表达中等水平 FcεRI 的细胞。这些 FcεRI(+)KIT(+)CD49b(-)细胞具有类似于腹腔结缔组织型 MC 的膜表型,但通过流式细胞术前向和侧向散射图谱分别显示出较小和低颗粒的特征。与之一致的是,它们缺乏通过组织化学和免疫检测鉴定的 MC 特异性颗粒蛋白酶的明显分泌颗粒,这些颗粒蛋白酶在成熟的空肠黏膜 MC 中很容易看到,并且也由感染诱导并同时存在。通过流式细胞术确定的 mLN 中这些 MC 谱系细胞的浓度与通过有限稀释和克隆扩增与成熟测量的 MC 祖细胞 (MCp) 的浓度相当。我们观察到 MCp 在 helminth 感染的 4get 小鼠的 mLN 和脾脏中 IL-4 转录的上调,并且通过细胞内细胞因子染色证明 helminth 感染小鼠的 mLN MCp 产生 IL-4 和 IL-6。此外,用抗 FcεRI mAb 治疗 helminth 感染的小鼠,该方案已知可耗尽嗜碱性粒细胞,也耗尽了 mLN MCp。因此,这项研究确定了一种在寄生虫感染时募集到 mLN 的低颗粒 MCp 亚群,它可能是一种未被认识到的重要细胞因子来源。