Induction of antigen-specific immunity and tolerance to Mycobacterium leprae in Lewis rats.

Induction of antigen-specific immunity and tolerance to Mycobacterium leprae in Lewis rats.
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Lewis 大鼠对麻风分枝杆菌的抗原特异性免疫和耐受性的诱导。

DOI:
10.1128/iai.58.2.495-501.1990
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发表时间:
1990
影响因子:
3.1
通讯作者:
Humphres,RC
Humphres,RC
中科院分区:
医学2区
文献类型:
--
作者:
Winters,MA;Humphres,RC

文献摘要

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用高压消毒麻风分枝杆菌对Lewis大鼠进行皮内免疫,可导致抗原特异性增殖反应和脾脏和淋巴结细胞释放白细胞介素-2,这种释放早在21天就可检测到,持续至少9个月,并且依赖于给药抗原的剂量。接种疫苗的动物也完全抵抗了带有活麻风分枝杆菌的足垫攻击。相反,静脉(i.v)给药至少10(8)个辐照麻风分枝杆菌分离株诱导无反应状态,其特征是抗原刺激淋巴细胞培养缺乏增殖和白细胞介素-2释放;然而,体外对有丝分裂刺激的反应以及体内对锁眼帽贝血青素和单核增生李斯特菌的反应均正常。接受麻风分枝杆菌静脉注射的动物即使在随后的免疫接种后仍对麻风分枝杆菌抗原无反应。这种无反应状态在诱导后至少持续了6个月。足垫攻毒实验结果表明,静脉注射麻风分枝杆菌后无反应的大鼠控制足垫内活麻风分枝杆菌生长的能力与未注射麻风分枝杆菌的大鼠无明显差异。此外,最初接受静脉注射和随后接受麻风分枝杆菌免疫接种的动物,与仅接受免疫接种的大鼠一样,不能免受可行的攻击。这些结果表明,大剂量麻风分枝杆菌静脉给药可诱导大鼠对麻风分枝杆菌抗原无反应,这可能与麻风型麻风患者的情况类似。
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.