Winters M A, Humphres R C
Cellular and Biochemical Technology Department, SRI International, Menlo Park, California 94025.
Infect Immun. 1990 Feb;58(2):495-501. doi: 10.1128/iai.58.2.495-501.1990.
Intradermal (i.d.) immunization of Lewis rats with autoclaved Mycobacterium leprae resulted in antigen-specific proliferation responses and interleukin-2 release from spleen and lymph node cells that were detectable as early as 21 days, persisted for at least 9 months, and were dependent on the dose of antigen administered. Immunized animals were also completely resistant to a footpad challenge with viable M. leprae. In contrast, intravenous (i.v.) administration of at least 10(8) irradiated M. leprae isolates induced a state of nonresponsiveness characterized by the absence of proliferation and interleukin-2 release by antigen-stimulated lymphoid cell cultures; however, in vitro responses to mitogenic stimulation and in vivo responses to keyhole limpet hemocyanin and Listeria monocytogenes were normal. Animals that received an i.v. injection of M. leprae remained nonresponsive to M. leprae antigens even after a subsequent i.d. immunization. This state of nonresponsiveness persisted for at least 6 months after induction. Results of footpad challenge experiments showed that the ability of animals rendered nonresponsive by an i.v. injection of M. leprae to control the growth of viable M. leprae in the footpad was not different from that of untreated rats. In addition, animals receiving an initial i.v. injection and a subsequent i.d. immunization with M. leprae were not protected from a viable challenge, as were rats that received only i.d. immunization. These results suggest that i.v. administration of a large dose of M. leprae to rats induces a state of nonresponsiveness to M. leprae antigens that may be similar to that seen in lepromatous leprosy patients.
用高压灭菌的麻风分枝杆菌对Lewis大鼠进行皮内免疫，可导致抗原特异性增殖反应以及脾脏和淋巴结细胞释放白细胞介素-2，最早在21天即可检测到，持续至少9个月，且依赖于所给予的抗原剂量。免疫动物对活的麻风分枝杆菌的足垫攻击也具有完全抗性。相比之下，静脉注射至少10⁸个经辐照的麻风分枝杆菌分离株可诱导一种无反应状态，其特征为抗原刺激的淋巴细胞培养物中无增殖和白细胞介素-2释放；然而，对丝裂原刺激的体外反应以及对匙孔血蓝蛋白和单核细胞增生李斯特菌的体内反应均正常。接受静脉注射麻风分枝杆菌的动物即使在随后进行皮内免疫后，对麻风分枝杆菌抗原仍无反应。这种无反应状态在诱导后持续至少6个月。足垫攻击实验结果表明，经静脉注射麻风分枝杆菌而变得无反应的动物控制足垫中活的麻风分枝杆菌生长的能力与未处理的大鼠无异。此外，接受初次静脉注射并随后进行皮内免疫的动物，与仅接受皮内免疫的大鼠不同，并未受到活菌攻击的保护。这些结果表明，给大鼠静脉注射大剂量的麻风分枝杆菌会诱导一种对麻风分枝杆菌抗原的无反应状态，这可能与瘤型麻风患者中所见的情况相似。
