Rosati E, Scaringi L, Cornacchione P, Fettucciari K, Sabatini R, Rossi R, Marconi P
Department of Clinical Medicine, University of Perugia, Policlinico Monteluce, Italy.
Cell Immunol. 1995 May;162(2):256-64. doi: 10.1006/cimm.1995.1077.
Inactivated Candida albicans (CA) cells induce strong activation of natural cytotoxic effectors in mice. In the present study we examined the expression of cytokine genes involved in the immune response to CA. It has been reported that differential cytokine production by natural immune cells is important for regulating the development of specific TH response. Northern blot analysis was performed on peritoneal exudate cells (PEC) recovered from CD2F1 mice injected ip with five doses of CA (CA-5d, on Days -14, -10, -7, -3, 0 with respect to the in vitro assays at 2, 24, and 72 hr) or from mice injected ip with four doses of CA (CA-4d, on Days -14, -10, -7, -3 with respect to the in vitro assay on Day 0). On Day 0, before the fifth CA injection, PEC expressed a high level of IL-2 and a low level of IL-1 beta mRNAs while genes coding for IL-4, IL-5, IL-6, IL-10, IL-12, TNF alpha, and IFN gamma were not expressed and there was a high level of NK activity. Two hours after CA-5d a high level of IFN gamma and a low level of IL-10 mRNAs were already evident, while IL-2 and much more IL-1 beta had greatly increased. IL-6, TNF alpha, and IL-2R alpha chain mRNAs were also detectable, whereas IL-4, IL-5, and IL-12 were not expressed. IL-12 mRNA was also absent in earlier stages of the CA sensitization. Both cellularity and NK activity of peritoneal exudate had increased with respect to Day 0. At 24 hr whereas IL-2 mRNA remained high, both IL-1 beta and IFN gamma mRNAs expression had decreased. Expression of other cytokines was no longer detectable but NK activity remained high and a significant LAK activity was also induced. After 72 hr, while the IL-2 mRNA level and NK activity were still high the IL-1 beta mRNA expression had further decreased. These results indicate that CA induces a predominant production of IFN gamma and IL-2, cytokines involved in the development of TH1 response but it is unable to induce IL-12. This secondary pathway, without IL-12 involvement in the development of TH1 response, is probably the result of the ability of IL-2, IL-1 beta, and TNF alpha to synergize in inducing IFN gamma synthesis by NK cells.
灭活白色念珠菌（CA）细胞可诱导小鼠体内自然细胞毒性效应细胞的强烈激活。在本研究中，我们检测了参与对CA免疫反应的细胞因子基因的表达。据报道，天然免疫细胞产生的不同细胞因子对于调节特异性TH反应的发展很重要。对从腹腔注射五剂CA（CA - 5d，相对于在第2、24和72小时进行的体外试验，于第 - 14、 - 10、 - 7、 - 3、0天注射）的CD2F1小鼠或腹腔注射四剂CA（CA - 4d，相对于第0天的体外试验，于第 - 14、 - 10、 - 7、 - 3天注射）的小鼠回收的腹腔渗出细胞（PEC）进行Northern印迹分析。在第0天，即第五次注射CA之前，PEC表达高水平的IL - 2和低水平的IL - 1β mRNA，而编码IL - 4、IL - 5、IL - 6、IL - 10、IL - 12、TNFα和IFNγ的基因未表达，且NK活性较高。CA - 5d注射后两小时，高水平的IFNγ和低水平的IL - 10 mRNA已经很明显，而IL - 2和更多的IL - 1β大大增加。IL - 6、TNFα和IL - 2Rα链mRNA也可检测到，而IL - 4、IL - 5和IL - 12未表达。在CA致敏的早期阶段也不存在IL - 12 mRNA。相对于第0天，腹腔渗出液的细胞数量和NK活性均增加。在24小时时，虽然IL - 2 mRNA仍然很高，但IL - 1β和IFNγ mRNA的表达均下降。其他细胞因子的表达不再可检测到，但NK活性仍然很高，并且还诱导了显著的LAK活性。72小时后，虽然IL - 2 mRNA水平和NK活性仍然很高，但IL - 1β mRNA的表达进一步下降。这些结果表明CA诱导主要产生IFNγ和IL - 2，这些细胞因子参与TH1反应的发展，但它不能诱导IL - 12。在TH1反应发展过程中没有IL - 12参与的这条次要途径，可能是IL - 2、IL - 1β和TNFα协同诱导NK细胞合成IFNγ能力所导致。
