Blackstock Rebecca, Murphy Juneann W
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, P.O. Box 26901, Oklahoma City, OK 73190, USA.
Infect Immun. 2004 Sep;72(9):5175-80. doi: 10.1128/IAI.72.9.5175-5180.2004.
Conflicting results have been reported regarding the ability of C57BL/6 mice to clear infections due to Cryptococcus neoformans. Examination of the various experimental protocols used suggested that C57BL/6 mice might develop the ability to resist infection as they mature. We analyzed the ability of C57BL/6 mice of different ages to respond to immunization with cryptococcal antigen or to clear a cryptococcal infection. Mice were immunized with a soluble cryptococcal culture filtrate antigen (CneF) emulsified in complete Freund's adjuvant (CneF-CFA). Delayed-type hypersensitivity (DTH) reactions elicited by the immunization were significantly stronger in 15-week-old C57BL/6 mice than in 7-week-old mice. Analysis of cryptococcal CFU 8 weeks following intratracheal infection of 7-week-old mice or 15-week-old mice revealed a relative inability of the younger animals to control the infection. Six-week-old immunized and infected mice cleared cryptococci from brain, spleen, and liver in a manner similar to that of immunized and infected 15-week-old mice. However, the older mice cleared cryptococci much more efficiently from the lungs. The possible role for NKT cells was determined by passive transfer of thymocytes from 10-week-old mice (containing mature NKT cells) or 2-week-old mice (containing immature NKT cells) to 6-week-old mice. The 10-week-old thymocytes significantly enhanced the ability of the mice to develop a DTH response after immunization with CneF-CFA, while animals treated with 2-week-old thymocytes did not improve their DTH response after immunization. The cells in the 10-week-old thymocyte population responsible for improvement of DTH responses were identified as being NK1.1 positive.
关于C57BL/6小鼠清除新型隐球菌感染的能力，已有相互矛盾的报道。对所使用的各种实验方案进行检查表明，C57BL/6小鼠可能会随着成熟而发展出抵抗感染的能力。我们分析了不同年龄的C57BL/6小鼠对隐球菌抗原免疫的反应能力或清除隐球菌感染的能力。用完全弗氏佐剂（CneF-CFA）乳化的可溶性隐球菌培养滤液抗原（CneF）对小鼠进行免疫。15周龄的C57BL/6小鼠免疫引发的迟发型超敏反应（DTH）明显强于7周龄小鼠。对7周龄或15周龄小鼠气管内感染8周后的隐球菌菌落形成单位（CFU）进行分析发现，年幼动物相对无法控制感染。6周龄免疫和感染的小鼠以类似于15周龄免疫和感染小鼠的方式从脑、脾和肝中清除隐球菌。然而，年长小鼠从肺部清除隐球菌的效率要高得多。通过将10周龄小鼠（含有成熟NKT细胞）或2周龄小鼠（含有未成熟NKT细胞）的胸腺细胞被动转移到6周龄小鼠来确定NKT细胞的可能作用。10周龄的胸腺细胞显著增强了小鼠在用CneF-CFA免疫后产生DTH反应的能力，而用2周龄胸腺细胞处理的动物在免疫后并未改善其DTH反应。10周龄胸腺细胞群体中负责改善DTH反应的细胞被鉴定为NK1.1阳性。
