Immunity in cutaneous leishmaniasis of the guinea-pig.

This paper describes the course of infection and development of immunity in guinea-pigs after intradermal inoculation of Leishmania enriettii, and the use of in vivo and in vitro techniques to characterize the immunological response to infection and artificial immunization. Inoculation of 10(6) amastigotes into the ear produced a nodule which ulcerated in 2–3 weeks and healed in 8–16 weeks. 8% of animals developed cutaneous metastases which healed with the original lesions. Histology of the primary lesions showed epidermal necrosis overlying a mass of parasitized macrophages which, after 4–6 weeks, became surrounded and infiltrated by lymphocytes. Histological changes in the draining lymph node began after 3 days and proceeded for 6 weeks; both germinal centres and paracortical areas were hyperplastic and the medulla contained many plasma cells. Superinfection produced an `isophasic' lesion, but reinfection after healing elicited only a delayed hypersensitivity response. Artificial immunization with soluble and insoluble antigenic extracts of L. enriettii in Freund's complete adjuvant partially protected against infection; extracts of other leishmanial species failed to protect. Immunological paralysis, attempted with intravenous injections of soluble antigen, increased the severity of subsequent infection. Both infection and immunization were accompanied by delayed hypersensitivity which could be transferred passively by lymphoid cells. Cell-mediated immunity was studied in vitro by the ability of soluble leishmanial antigens to transform lymphocytes, to inhibit macrophage migration, and to induce the production of lymphokine factors from lymphocytes of sensitized animals. A target cell system was devised in which sensitized lymphocytes destroyed monolayers of parasitized macrophages. Cross reactivity of leishmanial with mycobacterial antigens was shown in skin tests and in target cell destruction, but not in cell transfer or in the other cell culture systems. The phagocytic activity of peritoneal macrophages from recovered animals was increased for homologous but not for heterologous species of Leishmania; the growth of ingested organisms was not however reduced. Circulating antibodies were not demonstrated by passive cutaneous anaphylaxis, or by agglutination of antigen coated sheep erythrocytes, in the sera of infected or convalescent animals, although some convalescent animals showed active cutaneous anaphylaxis. However, antibodies were demonstrated by both these techniques in immunized animals, which also showed anaphylactic and Arthus hypersensitivity when skin tested with the soluble antigens. The results are taken to indicate that cellular mechanisms are prominent in the development of immunity of the guinea-pig against L. enriettii, and ways in which the host may eliminate the parasite are discussed. It is concluded that this model provides an experimental counterpart of human cutaneous leishmaniasis and that it is suitable for the analysis of the role of cell-mediated specific immunity in resistance to intracellular infection.