Fukushima Atsuki, Yamaguchi Tomoko, Fukuda Ken, Sumi Tamaki, Kumagai Naoki, Nishida Teruo, Imai Shosuke, Ueno Hisayuki
Department of Ophthalmology and Visual Science, Kochi Medical School, Japan.
Microbiol Immunol. 2006;50(9):719-28. doi: 10.1111/j.1348-0421.2006.tb03845.x.
Although CD4+ Th2 cells clearly play an essential role in the development of experimental allergic diseases, the functions CD8+ T cells may have in these diseases have been investigated less extensively and remain controversial. Here, we investigated the roles of CD8+ T cells in the development of experimental allergic conjunctivitis (EC). EC was induced in CD8alpha-deficient (CD8KO) mice and wild-type (WT) mice by active immunization with short ragweed pollen (RW) followed by challenge with RW-containing eye drops. Alternatively, EC was induced by transferring RW-primed splenocytes followed by RW challenge. With regard to actively immunized mice, CD8KO mice showed significantly less severe eosinophil infiltration of the conjunctiva and lower total IgE levels, although the levels of the other Igs were equivalent between the two strains. Cytokine production by cultured splenocytes also did not differ, but the WT conjunctivas showed upregulated IL-5 and IL-6 expression and greater upregulation of IL-4 expression than the conjunctivas of CD8KO mice. Thus, CD8+ T cells may play a significant role during the induction phase by aiding IgE production and the generation of Th2 cytokines in the conjunctiva, thus promoting the development of EC. In contrast, splenocytes from CD8KO mice induced significantly more severe EC in WT mice than cells from WT mice. In addition, transfer of RW-primed splenocytes induced significantly more severe eosinophil infiltration in CD8KO recipient mice. Thus, CD8+ T cells promote the development of EC during the induction phase, but suppress it during the effector phase.
尽管CD4+ Th2细胞在实验性过敏性疾病的发展中显然起着至关重要的作用,但CD8+ T细胞在这些疾病中可能具有的功能研究较少,且仍存在争议。在此,我们研究了CD8+ T细胞在实验性变应性结膜炎(EC)发展中的作用。通过用短豚草花粉(RW)主动免疫,然后用含RW的滴眼液激发,在CD8α缺陷(CD8KO)小鼠和野生型(WT)小鼠中诱导EC。或者,通过转移经RW致敏的脾细胞,然后进行RW激发来诱导EC。对于主动免疫的小鼠,尽管两品系之间其他免疫球蛋白的水平相当,但CD8KO小鼠结膜的嗜酸性粒细胞浸润明显较轻,总IgE水平较低。培养的脾细胞产生的细胞因子也没有差异,但WT小鼠结膜的IL-5和IL-6表达上调,且IL-4表达的上调程度高于CD8KO小鼠的结膜。因此,CD8+ T细胞可能在诱导期通过辅助结膜中IgE的产生和Th2细胞因子的生成发挥重要作用,从而促进EC的发展。相比之下,来自CD8KO小鼠的脾细胞在WT小鼠中诱导的EC比来自WT小鼠的细胞更严重。此外,转移经RW致敏的脾细胞在CD8KO受体小鼠中诱导的嗜酸性粒细胞浸润明显更严重。因此,CD8+ T细胞在诱导期促进EC的发展,但在效应期抑制它。