Johansson U, Sander B, Hultman P
Departments of Pathology, Linköping University, Linköping, Sweden.
J Autoimmun. 1997 Aug;10(4):347-55. doi: 10.1006/jaut.1997.0149.
Mercury induces a systemic autoimmune condition characterized by auto-antibodies to the nucleolar protein fibrillarin (AFA) and systemic immune-complex (IC) deposits in genetically susceptible mouse strains. This study examines T cell activation and cytokine production following mercury exposure in genetically susceptible and resistant strains. Mercury injected s.c., according to the protocol for induction of autoimmunity, caused an early T cell activation, measured as an increase of IL-2-producing cells, and increased expression of the IL-2-receptor proteins CD25 and CD122 and of the proliferation marker CD71 on days 2-4 in the susceptible A.SW and A. TH strains. This was followed by a long-lasting increase in the number of T cells, dominated by CD4(+) cells. Mice of the susceptible A.SW strain showed a modest increase of TNF-alpha-, IFN-gamma-, and IL-4-producing cells after 4-6 days, and a very distinct increase of IL-4-producing cells on days 8-10. The susceptible SJL strain (H-2(s)), severely deficient in Th2-promoting CD4(+), NK1.1(+) T cells, showed no increase of IL-4(+) cells on days 8-10. Instead, the number of IFN-gamma-producing cells was increased. Susceptible mice developed an increase of Ig-producing cells, AFA, and systemic IC-deposits. Genetically mercury-resistant A.TL mice showed a minimal increase of T cells, but no increase in cytokine-producing cells. We conclude that autoimmunogenic doses of HgCl2 induce an activation and proliferation of T cells in genetically susceptible mouse strains, as well as a broad increase of cytokine-producing cells, followed by a late predominance of the Th2-associated IL-4. One strain, severely deficient in Th2-promoting CD4(+), NK1.1(+) T cells, lacked the increase in IL-4(+) cells, indicating that a predominantly Th2-response is not necessary for induction of autoimmunity by mercury. However, a Th2-dominated response led to a faster and stronger B cell activation.
汞会在基因易感性小鼠品系中引发一种全身性自身免疫病症，其特征为针对核仁蛋白纤维原蛋白的自身抗体（AFA）以及全身性免疫复合物（IC）沉积。本研究检测了基因易感性和抗性品系在汞暴露后的T细胞活化及细胞因子产生情况。按照自身免疫诱导方案皮下注射汞后，在易感性A.SW和A.TH品系中，于第2至4天导致早期T细胞活化，表现为产生白细胞介素-2（IL-2）的细胞数量增加，以及IL-2受体蛋白CD25和CD122以及增殖标志物CD71的表达增加。随后是T细胞数量的持续增加，以CD4(+)细胞为主。易感性A.SW品系的小鼠在4至6天后，产生肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和IL-4的细胞数量有适度增加，在第8至10天产生IL-4的细胞数量有非常明显的增加。易感性SJL品系（H-2(s)）严重缺乏促进Th2的CD4(+)、NK1.1(+) T细胞，在第8至10天IL-4(+)细胞数量没有增加。相反，产生IFN-γ的细胞数量增加。易感性小鼠的产生免疫球蛋白的细胞、AFA和全身性IC沉积增加。基因抗汞的A.TL小鼠的T细胞仅有极小增加，但产生细胞因子的细胞没有增加。我们得出结论，自身免疫原性剂量的氯化汞在基因易感性小鼠品系中诱导T细胞活化和增殖，以及产生细胞因子的细胞广泛增加，随后Th2相关的IL-4在后期占主导。一个严重缺乏促进Th2的CD4(+)、NK1.1(+) T细胞的品系，缺乏IL-4(+)细胞的增加，这表明汞诱导自身免疫并不一定需要以Th2为主的反应。然而，以Th2为主的反应导致B细胞活化更快且更强。
