Bryceson A D, Bray R S, Dumonde D C
Clin Exp Immunol. 1974 Feb;16(2):189-202.
The purpose of this study was to determine whether suppression of acquired, cell-mediated immunity occurred during the course of cutaneous leishmaniasis of the guinea-pig. In order to do this, groups of animals were infected with amastigotes of in doses ranging from 10 to 2 × 10 organisms. The clinical course of primary and metastatic infection was followed for up to 30 weeks and the immunological response was examined by skin tests of hypersensitivity to soluble leishmanial antigens, by detection of circulating antibody, and by determining the resistance of animals to reinfection with fresh organisms. With increasing inoculum size the incubation period (for the establishment of a primary lesion) diminished from 4 weeks (10 organisms) to 1 week (2 × 10 organisms). Large inocula (2 × 10) led to large ulcerated primary lesions with widespread metastases and death of some animals in the group, but no evidence of visceralization. With increasing dose of organisms, there was increasingly rapid development of delayed hypersensitivity and of antibody as detected by immunofluorescence; thus there was no evidence that high inocula produced immunological tolerance. With inocula >10, a characteristic and selective depression of delayed hypersensitivity occurred when primary lesions were well developed and when metastatic infection was well advanced. Surviving animals recovered their delayed hypersensitivity as primary and metastatic lesions healed. After healing of the primary lesions, animals in all groups were fully resistant to reinfection, even though some of them bore persistent metastases. It was concluded that the immunosuppressive effects of heavy infecting inocula were due to desensitization of rapidly acquired, cell-mediated immunity rather than to the induction of immunological tolerance. It is suggested that this mechanism might underlie certain features of disseminated leishmaniasis in man.
本研究的目的是确定豚鼠皮肤利什曼病病程中是否发生获得性细胞介导免疫的抑制。为了做到这一点，将几组动物用10至2×10个生物体剂量的无鞭毛体进行感染。对原发性和转移性感染的临床病程进行了长达30周的跟踪，并通过对可溶性利什曼原虫抗原的超敏皮肤试验、检测循环抗体以及测定动物对新鲜生物体再感染的抵抗力来检查免疫反应。随着接种量的增加，潜伏期（形成原发性病变）从4周（10个生物体）缩短至1周（2×10个生物体）。大接种量（2×10）导致大的溃疡性原发性病变，伴有广泛转移，该组中的一些动物死亡，但无内脏化证据。随着生物体剂量的增加，通过免疫荧光检测到迟发型超敏反应和抗体的发展越来越快；因此，没有证据表明大接种量会产生免疫耐受。当接种量>10时，在原发性病变充分发展和转移性感染进展良好时，会出现迟发型超敏反应的特征性和选择性抑制。存活的动物随着原发性和转移性病变的愈合恢复了迟发型超敏反应。原发性病变愈合后，所有组的动物对再感染均具有完全抵抗力，即使其中一些动物有持续性转移。得出的结论是，大量感染接种物的免疫抑制作用是由于快速获得的细胞介导免疫的脱敏，而不是由于诱导免疫耐受。有人提出，这种机制可能是人类播散性利什曼病某些特征的基础。
