LEISHMANIA-AMAZONENSIS - THE ASIAN RHESUS MACAQUES (MACACA-MULATTA) AS AN EXPERIMENTAL-MODEL FOR STUDY OF CUTANEOUS LEISHMANIASIS

As a means of assessing the usefulness of the Rhesus macaque (Macaca m ulatta) as a nonhuman primate model for studying cutaneous leishmanias is, monkeys were infected with Leishmania amazonensis. Variation in th e level of susceptibility was found; however, animals inoculated with 10(8) promastigotes provided consistent results as indicated by an ear lier on set and/or larger size of lesions. Three monkeys, which had re covered from skin lesions, were challenge-infected using the same para site strain/dose; although these animals remained susceptible to homol ogous infection, lesion size was smaller and healed faster than in the initial infection. The immunologic features during infection were ass essed. Levels of IgM and IgG antibodies to promastigote antigens rose during active infection and then declined; immunoblot analyses indicat ed that numerous leishmanial antigens (predominately >30 kDa) were rec ognized. Delayed type hypersensitivity (DTH) responses and proliferati ve responses (PBL) developed during active infection and/or rechalleng e. Circulating peripheral T cell subpopulations varied throughout the course of infection. Initially (6-8 weeks p.i.). CD4+ T cells appear t o predominate; subsequently (15-21 weeks p.i), an increase in CD8+ T c ells was observed. Pathologic analyses indicated that lesions containe d amastigotes with a mononuclear infiltrate of macrophages, lymphocyte s, and plasma cells, and formation of tuberculoid-type granulomas. As the progression and resolution of leishmanial infection in rhesus maca ques are very similar to those observed in humans, this primate model could be employed for elucidating the mechanisms of protective immunit y in cutaneous leishmaniasis. (C) 1996 Academic Press, Inc.