Seo Keun Seok, Park Joo Youn, Davis William C, Fox Lawrence K, McGuire Mark A, Park Yong Ho, Bohach Gregory A
Microbiology, Molecular Biology and Biochemistry, University of Idaho, Moscow, ID 83844-2337, USA.
J Leukoc Biol. 2009 Apr;85(4):606-16. doi: 10.1189/jlb.0608338. Epub 2009 Jan 7.
Although many effects of staphylococcal superantigens (SAg) on T cells are well established, less is known about their effects on APC. In this study, bovine PBMC were stimulated with a low dose of staphylococcal enterotoxin C1 (SEC1). The phenotype of adherent cells (Ac) derived from bovine PBMC cultured with SEC1 [SEC1-stimulated Ac (sAc)] for 192 h was CD14(-), CD68(-), CD163(-), dendritic cell (DC)-specific ICAM-3-grabbing nonintegrin(+), MHC class II (MHC II)(high), CD11a(low), CD11b(high), CD11c(high), and CD1b(high), suggesting these cells were dendritic cells (DC). SEC1 also induced transcription of the CXCL1, -2, and -3 family, CXCL6, CCL2, and CCL5 genes in sAc, which increased rapidly but returned to basal levels by 48 h. In contrast, increased transcription of CCL3, CCL8, and CXCL12, responsible for mononuclear cell migration and chronic inflammation, was sustained. In vitro cell migration assays showed vigorous migration of granulocytes, followed by migration of mononuclear cells. The autologous MLR showed that sAc induced a dose-dependent proliferation of CD4(+) T cells and an even stronger proliferation of CD8(+) T cells. This effect was inhibited or reduced by pretreatment with mAb to CD11b, MHC II, or MHC II plus CD18. These results indicate that stimulation of bovine PBMC by SAg induces differentiation of monocytes into DC.
尽管葡萄球菌超抗原(SAg)对T细胞的许多作用已得到充分证实,但关于它们对抗原呈递细胞(APC)的作用却知之甚少。在本研究中,用低剂量的葡萄球菌肠毒素C1(SEC1)刺激牛外周血单核细胞(PBMC)。将与SEC1一起培养192小时的牛PBMC来源的贴壁细胞(Ac)[SEC1刺激的Ac(sAc)]的表型鉴定为CD14(-)、CD68(-)、CD163(-)、树突状细胞(DC)特异性细胞间黏附分子3结合非整合素(+)、主要组织相容性复合体II类(MHC II)(高)、CD11a(低)、CD11b(高)、CD11c(高)和CD1b(高),表明这些细胞是树突状细胞(DC)。SEC1还诱导sAc中CXCL1、-2和-3家族、CXCL6、CCL2和CCL5基因的转录,这些基因迅速增加,但在48小时时恢复到基础水平。相反,负责单核细胞迁移和慢性炎症的CCL3、CCL8和CXCL12的转录增加则持续存在。体外细胞迁移试验显示粒细胞有活跃的迁移,随后是单核细胞的迁移。自体混合淋巴细胞反应(MLR)表明,sAc诱导CD4(+)T细胞呈剂量依赖性增殖,CD8(+)T细胞增殖更强。用抗CD11b、MHC II或MHC II加CD18单克隆抗体预处理可抑制或降低这种作用。这些结果表明,SAg刺激牛PBMC可诱导单核细胞分化为DC。