Experimental cutaneous leishmaniasis. IV. Selective suppression of cell-mediated immunity during the response of guinea-pigs to infection with Leishmania enriettii

Abstract

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 Leishmania enriettii in doses ranging from 10¹ to 2 × 10⁸ 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 (10¹ organisms) to 1 week (2 × 10⁸ organisms). Large inocula (2 × 10⁸) 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 >10⁵, 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.