Bryceson A D, Preston P M, Bray R S, Dumonde D C
Clin Exp Immunol. 1972 Feb;10(2):305-35.
Intradermal inoculation of the guinea-pig with results in a self-healing cutaneous lesion which provides a laboratory model of human cutaneous leishmaniasis and which is dominated by cell-mediated immunological responses (Bryceson ., 1970). In this study we sought to design experimental situations resembling non-healing forms of cutaneous leishmaniasis in man and to determine whether these experimental situations were accompanied by abnormalities in the immunological response to infection. This paper describes three procedures which impair the resistance of guinea-pigs to leishmanial infection: (i) induction of partial immunological tolerance to leishmanial antigen; (ii) systemic injection of anti-lymphocyte serum (ALS); and (iii) regional antigenic competition produced by multiple injections of bacterial adjuvants. Injection of soluble leishmanial antigen (PSA) during the third week of foetal life suppressed resistance to neonatal infection with ; local infections were severe and were accompanied by metastatic spread and by impaired development of delayed hypersensitivity (DH). Injection of PSA into the 6-week foetus and into the adult guinea-pig led to impaired DH after leishmanial infection, but resistance to infection was only slightly suppressed. Transient impairment of DH was induced by a short injection course of adult animals with ALS during the first 3 weeks of infection, which resulted in large primary lesions with temporary metastatic spread. Multiple regional injections of tubercle- and corynebacterial-adjuvant emulsions markedly suppressed resistance to subsequent leishmanial infection; large ulcerative lesions were accompanied by widespread nodular metastases, the unusual appearance of haemagglutinating antibody, and death of some animals. There was no impairment of DH to PSA; in fact, this was temporarily enhanced during the first 6 weeks of leishmanial infection of the tubercle-adjuvant group. This suppression of resistance could not be attributed to systemic desensitization of DH to bacterial antigen or to the local sclerosing effects of adjuvant emulsion; the term `regional antigenic competition' was therefore employed. Both the induction of partial tolerance and the injection of ALS selectively impaired paracortical responses in lymph nodes draining leishmanial infections; however, in regional antigenic competition the lymph nodes were infiltrated with macrophages but both follicular and paracortical responses were prominent. Suppression of resistance to was not related simply to impairment of DH; for there was overall dissociation of protective, allergic and antibody responses in these suppressed animals. The relationship of cellular immune mechanisms to cutaneous leishmaniasis was viewed in two ways. First, it was inferred that resistance of guinea-pigs to requires both successful induction of cell-mediated immunity and functional integrity of the regional lymphoid system at the time of infection. Second, it was suggested that nonhealing forms of human cutaneous leishmaniasis may arise from defective coordination of surveillance, inflammatory and adjuvant functions of the cellular immune response to leishmanial antigens. It was concluded that interference with cellular immune responses in the guinea-pig led to experimental infections which resembled some features of more generalized cutaneous leishmaniasis in man.
用……对豚鼠进行皮内接种会导致一种自愈性皮肤病变，这提供了人类皮肤利什曼病的实验室模型，且该模型以细胞介导的免疫反应为主（布莱森等人，1970年）。在本研究中，我们试图设计类似于人类皮肤利什曼病非愈合形式的实验情况，并确定这些实验情况是否伴随着对感染的免疫反应异常。本文描述了三种损害豚鼠对利什曼原虫感染抵抗力的方法：（i）诱导对利什曼原虫抗原的部分免疫耐受性；（ii）全身注射抗淋巴细胞血清（ALS）；（iii）多次注射细菌佐剂产生的局部抗原竞争。在胎儿生命的第三周注射可溶性利什曼原虫抗原（PSA）会抑制对新生儿感染……的抵抗力；局部感染严重，伴有转移扩散和迟发型超敏反应（DH）发育受损。在6周龄胎儿和成年豚鼠中注射PSA会导致利什曼原虫感染后DH受损，但对感染的抵抗力仅略有抑制。在感染的前三周对成年动物进行短疗程的ALS注射可诱导DH的短暂损害，这导致大的原发性病变并伴有暂时的转移扩散。多次局部注射结核杆菌和棒状杆菌佐剂乳剂可显著抑制对随后利什曼原虫感染的抵抗力；大的溃疡性病变伴有广泛的结节性转移、血凝抗体的异常出现以及一些动物的死亡。对PSA的DH没有损害；事实上，在结核杆菌佐剂组利什曼原虫感染的前6周内，这种反应暂时增强。这种抵抗力的抑制不能归因于对细菌抗原的DH全身脱敏或佐剂乳剂的局部硬化作用；因此采用了“局部抗原竞争”这一术语。诱导部分耐受性和注射ALS均选择性地损害了引流利什曼原虫感染的淋巴结中的皮质旁反应；然而，在局部抗原竞争中，淋巴结有巨噬细胞浸润，但滤泡和皮质旁反应均很突出。对……感染抵抗力的抑制不仅仅与DH的损害有关；因为在这些受抑制的动物中，保护性、过敏性和抗体反应总体上是分离的。细胞免疫机制与皮肤利什曼病的关系从两个方面来看待。首先，据推断豚鼠对……的抵抗力既需要成功诱导细胞介导的免疫，又需要感染时局部淋巴系统的功能完整性。其次，有人提出人类皮肤利什曼病的非愈合形式可能源于对利什曼原虫抗原的细胞免疫反应的监测、炎症和佐剂功能的协调缺陷。得出的结论是，干扰豚鼠的细胞免疫反应会导致实验性感染，这些感染类似于人类更广泛的皮肤利什曼病的一些特征。
