Antigen-specific immunodeficiency and its relation to the spectrum of American cutaneous leishmaniasis

Delayed-type hypersensitivity (DTH) and antibodies against Leishmania have been studied in 207 Venezuelan patients with localized, muco-cutaneous and diffuse forms of American cutaneous leishmaniasis, representing the clinical spectrum of this disease. Muco-cutaneous disease appears to be related to inadequate immunomodulation or defective killing mechanisms; about 40% of these patients show exaggerated DTH, which is inversely related to antibody levels and is more pronounced in less extensive lesions. Patients with diffuse disease present severe antigen-specific immunodeficiency, apparently limited to T cell-mediated protection, DTH and its in vitro correlates. Treatment of patients with diffuse cutaneous leishmaniasis using a combination of chemotherapy and combined vaccine immunotherapy (heat-killed promastigotes plus BCG) has induced clinical inactivity and positive DTH in about one third of these patients, accompanied by marked lowering of antibody levels. These results are discussed in terms of Type 1 T cell responses, protective in cell-mediated immune reactions, and Type 2 T cell responses, non-protective in cell-mediated reactions, in the spectrum of leishmaniasis. Factors related to the induction of favorable Type 1 responses to intracellular pathogens are discussed in terms of a possible mechanism of the combined vaccine efficacy and priorities in vaccine development.