Tanaka T, Katada Y, Higa S, Fujiwara H, Wang W, Saeki Y, Ohshima S, Okuda Y, Suemura M, Kishimoto T
Department of Medicine III, Osaka University Medical School, 202 Yamada-oka Suita City, Osaka 565-0871, Japan.
Cytokine. 2001 Feb 21;13(4):193-201. doi: 10.1006/cyto.2000.0828.
Functional roles of interleukin (IL-)6 in T cell response were investigated. Mice deficient in IL-6 and wild mice were immunized with antigens (myelin oligodendrocyte glycoprotein or methylated BSA) and production of IL-4 and interferon (IFN)-gamma by regional lymph nodes was measured. IL-6 deficiency led to an enhancement of IL-4 and an inhibition of IFN-gamma production. Moreover, polyclonal stimulation of spleen T cells from unimmunized IL-6-deficient mice with anti-CD3 plus anti-CD28 antibodies (Abs) demonstrated an enhancement of T helper (Th)(2)responses. The presence of IL-6, however, augmented IL-4 production but it inhibited IFN-gamma expression by spleen T cells in response to polyclonal stimulation and by antigen-primed spleen T cells in response to re-challenge with the antigen. In contrast, the induction of spleen CD4-positive T cells into Th(2)cells in vitro by the anti-CD3 plus IL-4 was completely suppressed by exogenously added IL-6, whereas Th(1)differentiation of T cells by the anti-CD3 plus IL-12 was not inhibited by the presence of IL-6. Thus, these results indicate that IL-6 physiologically could modulate qualitative T cell response and suggest that it augments Th(1)responses partly through its inhibitory capability of IL-4-induced Th(2)differentiation of naive T cells.
研究了白细胞介素（IL-）6在T细胞反应中的功能作用。用抗原（髓鞘少突胶质细胞糖蛋白或甲基化牛血清白蛋白）免疫IL-6缺陷小鼠和野生型小鼠，并测量局部淋巴结中IL-4和干扰素（IFN）-γ的产生。IL-6缺陷导致IL-4产生增强和IFN-γ产生受到抑制。此外，用抗CD3加抗CD28抗体（Abs）对未免疫的IL-6缺陷小鼠的脾T细胞进行多克隆刺激，显示辅助性T（Th）（2）反应增强。然而，IL-6的存在增加了IL-4的产生，但它抑制了脾T细胞在多克隆刺激下以及抗原致敏的脾T细胞在再次接触抗原时的IFN-γ表达。相反，抗CD3加IL-4在体外将脾CD4阳性T细胞诱导为Th（2）细胞的过程被外源性添加的IL-6完全抑制，而抗CD3加IL-12诱导T细胞向Th（1）分化则不受IL-6存在的抑制。因此，这些结果表明IL-6在生理上可以调节T细胞的定性反应，并提示它部分通过其抑制IL-4诱导的幼稚T细胞向Th（2）分化的能力来增强Th（1）反应。
