[Immunopathology of American tegumentary leishmaniasis]

The complex cell mediated immune response in parasitic diseases can be evaluated in different body compartments. In the present work we describe the results of studies of peripheral blood lymphocytes and the cutaneous lesions in the three clinical forms of tegumentary leishmaniasis. These clinical forms, that constitute a clinical, histological and immunological spectrum, are: localized cutaneous leishmaniasis (LCL), diffuse cutaneous (DCL9, and the intermediate forms that include mucous and verrocous leishmaniasis (MCL). The overall results suggest that the cytokine pattern of lymphocytes in the blood and lesions of LCL, the self-limiting form of the disease, is T-helper type 1. This leads to the cure of the lesions in these patients, either spontaneously or after appropriate therapy. The disseminated disease in DCL patients is resistant to chemotherapy, and is characterized by a Th2 cytokine pattern, with a an absence of IL-2 AND ifn-gamma production when the lymphocytes are specifically stimulated by leishmanial antigen. This is probably why these patients are unable to control the infection, and allows the cutaneous dissemination of the parasite. The intermediate MCL form is characterized by destructive lesions of the oral and nasopahryngeal mucosas, with a tendency to the chronicity of the infection. The cytokine pattern of MCL patients is a mixture of Type 1 and Type 2 responses. This may be responsible for the progression of the disease in these patients, as it is possible that when both types of cytokines are produced, the Type 2 responses can predominate over the Type 1 and the disease is maintained in a chronic, although activated, state. The examination of the cutaneous lesions demonstrated that the epidermis in the DCL lesions is deficient in ICAM-1 accessory signals and MHC-II expression by keratinocytes, and presents a variable number of Langerhans cells. In MCL lesions, the expression of ICAM-1 and MHC-II is elevated, and Langerhans cells are absent in the damaged epithelium. The epidermis of LCL lesions show ICAM-1 in patches and MHC uniformly expressed by keratinocytes. DCL lesions are characterized by low CD4/CD8 and memory/naive T cell ratios, low numbers of T gamma delta cells, and an apparent defect in the expression of LFA-1 directional receptors. The cytokine patterns are Th1 and Th2, with the latter predominating. MCL granulomas manifest high CD4/CD8 and memory/naive Tcel ratios, low numbers of T gamma delta, a high coefficients of cellular adhesion, with a mixed Th1/Th2 cytokine pattern. LCL granulomas are characterized by a normal CD4/CD8 ratio, a high memory/naive cell ratio, numerous groups of T gamma delta, a high expression of directional receptors, and Th1/Th0 cytokine patterns. We discuss the results in the context of the immunological effects, both in immunotherapy and immunoprophylasis, of the combined vaccine of BCG plus promastigotes of Leishmania. In immunotherapy we demonstrate that the combined vaccine simulates a Th1 response in LCL patients. As an immunoprophylactic vaccine in healthy individuals from an endemic area of leishmaniasis, it stimulates a Th1 response (positivity in the Montenegro cutaneous reactions, proliferative responses in vitro and production of IFN-gamma), with a low specific antibody response. This demonstrates that the combined vaccine is potentially useful both in the treatment of LCL patients, as well as being potentially protective applied as immunoprophylaxis in the control of leishmaniasis.