Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica
Immunological regulation of experimental cutaneous leishmaniasis. III. Nature and significance of specific suppression of cell-mediated immunity in mice highly susceptible to Leishmania tropica
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实验性皮肤利什曼病的免疫调节。
DOI：
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发表时间：
1980
影响因子：
15.3
通讯作者：
F. Liew
中科院分区：
文献类型：
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作者：
J. Howard;C. Hale;F. Liew
BALB/c小鼠对热带利什曼原虫感染具有特殊的易感性，使得皮肤病变在所有情况下无限制地生长，导致正常和X射线照射的骨髓重建（XBM）动物中的致命转移和内脏化。然而，成年胸腺切除、X射线照射、骨髓重建（ATxXBM）的BALB/c小鼠表现出明显的病变生长迟缓，导致一些存活甚至治愈。在中度易感（BALB/c X C57 BL/6）F1小鼠中也发现了类似的趋势，与“耐药”CBA品系相反，如前所述，ATxXBM动物显示正常的自发自愈功能受损。这些转化效应被相应的利什曼特异性迟发型超敏反应（DTH）反应性所证实，在BALB/c和（BALB/c X C57 BL/6）F1中，先前的胸腺切除导致CBA减少和增加。抗利什曼原虫DTH反应，可通过环磷酰胺预处理放大，在BALB/c小鼠中在感染2 × 10（7）前鞭毛体10天内可检测到，但在第25-35天几乎完全被抑制。在CBA、C57 BL/6或（BALB/c × C57 BL/6）F1小鼠中没有发现这种抑制作用，同时发现对病变发展或消退有不同程度的免疫控制。在BALB/c小鼠中，DTH的抑制是利什曼原虫特异性的，并且不限于2，4-二硝基氟苯（DNFB）或绵羊红细胞特异性。抑制L.当转移到正常BALB/c小鼠时，Tropica感染的小鼠损害了对利什曼原虫抗原的DTH诱导。这种性质存在于T细胞富集的级分中，而不是T细胞耗尽的级分中。结论：BALB/c小鼠对L.热带病感染涉及通过抑制性T细胞产生对潜在治愈性细胞介导的免疫应答的严重损害。可能性进行了讨论，这可能是继发于快速无鞭毛体（抗原）积累在巨噬细胞表达的主要遗传“缺陷”。"
BALB/c mice have been an exceptional susceptibility to Leishmania tropica infection such that cutaneous lesions grow without restraint in all cases leading to fatal metastasis and visceralization in normal and x-irradiated, bone-marrow reconstituted (XBM) animals. Adult thymectomized, x-irradiated, bone marrow-reconstituted (ATxXBM) BALB/c mice, however, show pronounced retardation of lesion growth leading to some survival and even cures. A similar trend was also found in moderately susceptible (BALB/c X C57BL/6)F1 mice, in contrast with the "resistant" CBA strain, in which, as previously known, ATxXBM animals showed impairment of normal, spontaneous self-healing. These convere effects are paralleled by respective leishmania-specific delayed-type hypersensitivity (DTH) reactivities, prior thymectomy leading to diminution in CBA and augmentation in BALB/c and (BALB/c X C57BL/6)F1. Anti-leishmanial DTH responses, amplfiable by cyclophosphamide pretreatment, can be detected in BALB/c mice within 10 d of infection with 2 X 10(7) promastigotes, but becomes near-totally suppressed by day 25-35. No such suppressin is found in CBA, C57BL/6, or (BALB/c X C57BL/6)F1 mice together with varying degrees of immune control of lesion development or regression. Suppression of DTH in BALB/c mice is leishmania specific and does not extent to 2,4-dinitrofluorobenzene (DNFB) or sheep erythrocytes specificities. Spleen cells from suppressed L. tropica-infected mice when transferred to normal BALB/c mice impaired the induction of DTH to leishmanial antigen. This property resided in the T cell-enriched fraction and not in the T cell- depleted fraction. It is concluded that a major component of the striking inability of BALB/c mice to control L. tropica infection involves profound impairment of a potentially curative cell-mediated immune response by suppressor T cell generation. The possibility is discussed that this may be secondary to rapid amastigote (antigen) accumulation in macrophages expressing the primary genetic "defect."