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This study shows how infection of CBA mice with L. tropica can be manipulated so as to mimic the principal features of both subclinical and self-healing cutaneous leishmaniasis in man. CBA mice were infected with graded inocula of L. tropica promastigotes. The pattern of primary infection was found to be dependent on dose of infecting organisms: mice given low dose inocula (10(2), 10(3)) developed subclinical infections; those given high dose inocula (10(4), 10(5), 10(6)) developed overt, clinical lesions. Size and duration of lesions, and antibody production were directly proportional to dose; delayed hypersensitivity responses were inversely proportional to dose. Protective immunity to challenge infection was induced by both subclinical and clinical infection; and was manifest both during and after the healing stages of primary lesions. Protective immunity was also induced by artificial immunization with sonicated promastigotes in adjuvants but was only manifest if the challenge dose was not too large. The course of challenge infections differed depending on the method of immunization, i.e. whether by infection or artificial immunization. Lymphoid cells from immune CBA mice conferred protection on recipient syngeneic CBA mice against challenge infection; serum from immune mice did not, but suspension of immune peritoneal cells in immune serum enhanced their protective capacity. The experimental induction of protective immunity by low-dose infection, without a clinical allergic response at the site of inoculation, is of importance in designing an immunoprophylactic approach to human leishmaniasis.

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.

Partial purification of soluble products of guinea-pig lymphocyte activation (LAP) was undertaken by fractional precipitation with ammonium sulphate, ion-exchange and Sephadex chromatography, and by immune precipitation of inducing antigen and of contaminating serum protein. During these purification steps the activity of macrophage migration-inhibition factor (MIF) was concentrated up to 1300-fold and separated from inducing antigen and serum protein. An endpoint assay was devised for expressing antigen-induced MIF activity of LAP fractions as weights of material giving 30% inhibition of migration (MI30 doses).

The experiments reported here were concerned with determining the effects of lymphocyte activation products (LAP) on lymph node architecture, and with assaying afferent lymph for evidence of the peripheral release of LAP during the induction of an immune response.