作者:L. J. Wheat、M. Durkin、C. Schnizlein-Bick、E. Bassey、S. Kohler、P. Connolly、J. Goldberg、T. Garringer、E. Brizendine、E. K. Thomas
DOI:10.1080/mmy.40.5.501.505
日期:2002.1
CD40 ligand-CD40 ligation is important in the development of T-cell-mediated immune responses. The purpose of this study was to examine the role of CD40L in recovery from histoplasmosis using a murine model of intratracheally induced infection. B6C3F1 mice were infected intratracheally with Histoplasma capsulatum yeast and monitored for clearance of the organism from the lungs and spleen. CD40L treatment was begun on either day −2 or +2 post inoculation and continued until day 14 in CD4-depleted animals and from day −2 to day +4 in nonimmunosuppressed animals. Amphotericin B treatment was begun four days following inoculation and given every other day for 10 days. CD40L reduced fungal burden by less than one log when started two days before infection but did not act synergistically with low-dosage amphotericin B (0.2 mg kg−1 qod) in CD4 depleted mice. Low-dose amphotericin B, CD40L, and the combination of the two failed to lower the fungal burden in a second experiment using a more virulent isolate of the same strain of H. capsulatum in CD4-depleted mice. Furthermore, CD40L did not increase the concentrations of IFN-γ, IL-12 or IL-10 in the lungs or spleens of infected animals. In summary, CD40L had minimal or no effect on the course of infection in this murine model of histoplasmosis.
CD40 配体-CD40 连接在 T 细胞介导的免疫反应发展过程中非常重要。本研究的目的是利用气管内诱导感染的小鼠模型,研究 CD40L 在组织胞浆菌病康复中的作用。B6C3F1 小鼠气管内感染荚膜组织胞浆酵母菌,并监测肺部和脾脏中病原体的清除情况。CD40L治疗从接种后第-2天或第+2天开始,CD4缺失动物的治疗持续到第14天,非免疫抑制动物的治疗从第-2天持续到第+4天。两性霉素 B 治疗从接种后四天开始,隔天一次,持续 10 天。在感染前两天开始使用 CD40L,可使真菌负担减少不到一个对数,但在 CD4 贫化的小鼠中,CD40L 与低剂量两性霉素 B(0.2 mg kg-1 qod)并无协同作用。在使用同一菌株中毒性更强的分离株对去掉 CD4 的小鼠进行的第二次实验中,低剂量两性霉素 B、CD40L 和两者的组合均未能降低真菌负荷。此外,CD40L并未增加受感染动物肺部或脾脏中IFN-γ、IL-12或IL-10的浓度。总之,CD40L对这种组织胞浆菌病小鼠模型的感染过程影响极小或没有影响。