Lundy Steven K, Boros Dov L
Department of Immunology and Microbiology, Wayne State University, School of Medicine, Detroit, Michigan 48201.
Infect Immun. 2002 Feb;70(2):812-9. doi: 10.1128/IAI.70.2.812-819.2002.
A previous study of the murine model of Schistosoma mansoni infection has implicated splenic CD19(+) B lymphocytes as Fas ligand (FasL)-bearing mediators of CD4(+) T-lymphocyte apoptosis. The present study shows that B-cell deficiency leads to decreased CD4(+) T-cell apoptosis during infection and compares FasL expression and killer function of B-1a- and CD5(-) B-lymphocyte subsets. B-1a cells from uninfected mice displayed constitutive expression of FasL compared with that of CD5(-) B cells. FasL expression was enhanced following worm egg deposition and antigenic stimulation on both subsets of B cells. Purified B-1a cells from uninfected mice were potent effectors of CD4(+) T-cell apoptosis, and the killing effect was enhanced during schistosome infection. FasL expression by splenic B cells required CD4(+)-T-cell help that was replaced by addition of culture supernatants from antigen-stimulated splenocytes of infected mice. The culture-supernatant-stimulated FasL expression was inhibited by anti-interleukin 10 (IL-10) and anti-IL-4 antibodies. Culture of purified B cells with recombinant IL-4 (rIL-4), rIL-10, and soluble egg antigens (SEA) led to increased expression of FasL on B-1a cells. These results suggest that FasL-expressing, splenic B-1a cells are important mediators of SEA-stimulated CD4(+)-T-cell apoptosis and that maximal FasL expression on B-1a cells is dependent on antigenic stimulation and the presence of IL-4 and IL-10.
先前一项关于曼氏血吸虫感染小鼠模型的研究表明,脾脏CD19(+) B淋巴细胞是携带Fas配体(FasL)的CD4(+) T淋巴细胞凋亡介质。本研究表明,B细胞缺陷会导致感染期间CD4(+) T细胞凋亡减少,并比较了B-1a和CD5(-) B淋巴细胞亚群的FasL表达及杀伤功能。与CD5(-) B细胞相比,未感染小鼠的B-1a细胞呈现FasL的组成性表达。在虫卵沉积和抗原刺激后,两个B细胞亚群的FasL表达均增强。未感染小鼠的纯化B-1a细胞是CD4(+) T细胞凋亡的有效效应细胞,且在血吸虫感染期间杀伤作用增强。脾脏B细胞的FasL表达需要CD4(+) T细胞的辅助,而添加感染小鼠抗原刺激脾细胞的培养上清液可替代这种辅助。抗白细胞介素10(IL-10)和抗IL-4抗体可抑制培养上清液刺激的FasL表达。用重组IL-4(rIL-4)、rIL-10和可溶性虫卵抗原(SEA)培养纯化的B细胞,可导致B-1a细胞上FasL表达增加。这些结果表明,表达FasL的脾脏B-1a细胞是SEA刺激的CD4(+) T细胞凋亡的重要介质,且B-1a细胞上FasL的最大表达依赖于抗原刺激以及IL-4和IL-10的存在。