Kerckhaert J A, Hofhuis F M, Willers J M
Immunology. 1977 Jun;32(6):1027-32.
The effect of a single dose of cyclophosphamide (CY) on delayed type hypersensitivity (DH) and acquired cellular resistance (ACR) to Listeria monocytogenes infection in mice was studied. Intraperitoneal or intracutaneous immunization with L forms of L. monocytogenes did not result in protection against lethal challenge. A positive DH could be observed when CY-treated mice were intracutaneously immunized with 10(8) or more L forms. Intraperitoneal injection of viable L. monocytogenes resulted only in a narrow dose range in survival on immunization and partial protection on challenge. Protection was accompanied by DH. Intracutaneous injection of Listeria in Freund's complete adjuvant permitted the use of even 10(9) viable bacteria for immunization. This figure was reduced to 10(5) or less for CY treated mice. In normal mice protection was afforded on immunization with 10(7) bacteria whereas 10(3) bacteria were sufficient to protect CY treated animals. All protected mice showed a positive DH. These results demonstrate that CY treatment reduces the dose of viable bacteria tolerated for immunization 10(4) times. On the other hand after CY treatment the doses of bacteria effective on immunization for ACR and DH could be reduced in the same order of magnitude. Reduction of the CY dose resulted in a peak DH with 4 mg CY, but the protection was less than that obtained after treatment with 6 mg CY. A dissociation between ACR and DH was observed by varying the interval between immunization and challenge. In normal mice DH was preceded by ACR, with peaks at respectively 10 and 5 days after immunization. CY treatment caused a delay in the onset of the ACR, followed by an enhanced and slightly prolonged response. The effect of CY on DH consisted of enhancement and prolongation.
研究了单剂量环磷酰胺（CY）对小鼠迟发型超敏反应（DH）和获得性细胞抗李斯特菌感染能力（ACR）的影响。用单核细胞增生李斯特菌的L型进行腹腔或皮内免疫，不能提供针对致死性攻击的保护作用。当用CY处理过的小鼠皮内接种10⁸或更多的L型菌时，可观察到阳性DH反应。腹腔注射活的单核细胞增生李斯特菌，仅在免疫时的一个狭窄剂量范围内能使小鼠存活，并在攻击时提供部分保护作用。这种保护作用伴随着DH反应。在弗氏完全佐剂中皮内注射李斯特菌，即使使用10⁹活细菌进行免疫也可行。对于用CY处理过的小鼠，这个数字降至10⁵或更少。在正常小鼠中，用10⁷细菌免疫可提供保护作用，而10³细菌就足以保护用CY处理过的动物。所有受保护的小鼠都表现出阳性DH反应。这些结果表明，CY处理可使免疫时耐受的活细菌剂量降低10⁴倍。另一方面，CY处理后，对ACR和DH有效的免疫细菌剂量可按相同数量级降低。CY剂量降低导致4mg CY时出现DH峰值，但保护作用小于6mg CY处理后获得的保护作用。通过改变免疫和攻击之间的间隔时间，观察到ACR和DH之间的分离现象。在正常小鼠中，DH反应之前有ACR反应，分别在免疫后10天和5天达到峰值。CY处理导致ACR反应开始延迟，随后反应增强且略有延长。CY对DH的影响包括增强和延长。
