American cutaneous leishmaniasis is characterized by a spectrum of clinical manifestations. These include localized, often self-healing single lesions, intermediate forms which frequently produce mucosal lesions and often show exaggerated delayed-type hypersensitivity (DTH), and the rare diffuse cutaneous leishmaniasis in which no reaction of protective cell-mediated immunity or DTH can be demonstrated. Clinical, pathological and immunological studies have begun to unravel some of the mechanisms associated with different disease manifestations, dependent on complex interactions between the host immune response, measured in terms of indices including lymphocyte subsets and lymphokines in vitro and within active lesions, and different species of Leishmania.

SUMMARYThe lymphokine profiles were dclermined in the skin lesions ol" ihe three distinct clinical forms of American cutaneous leishmaniasis (ACL), using a reverse transcriptase polymerase chain rcaclion (RT-PCR) and primers for various lymphokines. The message for interferon-gamma (IFN-y). lumour necrosis factor-beta (TNF-/i). and lL-8 was expressed in the three clinical forms of ACL. IL-l//niRNA was expressed in most localized (LCL) and miicocutaneous (MCL) leishmaniasis. but in only few ofthe diffuse cutaneous leishmaniasis (DCL). IL-2 mRNA was detected in ahoui half of the lesions, with more prominent values for MCL. IL-4 niRNA was present in most lesions from the three clinical forms, but markedly increased in DCL. IL-5 and IL-IO mRNAs were expressed in all MCL and in half of the DCL lesions and weakly expressed in LCL lesions. IL-IO mRNA was more abundant in MCL lesions. In contrast. IL-6 and TN F-x mRNAs were expressed in a large number of LCL-In MCL, IL-6 mRNA was expressed in most cases and TNF-ct mRNA in alt the cases. In DCL, IL-6 mRNA was absent and TNF-a mRNA was weakly expressed. These results suggest that most T cells present in the MCL and DCL lesions secrelc a mixture of type 1 and type 2 cytokine patterns, but in DCLgranulomas type 2 cytokines predominate. In LCL the cytokine patterns show a mixture of type 1 and type 0 with a preponderance of IFN-; over iL-4. and low levels of lL-5 and IL-IO. The lack of IL-6 and TNF-a mRNAs, and the low expression of IL-lfi in DCL lesions suggest a defect in the antigen-processing eells that may account for the state of unresponsiveness in these patients.

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Accessory signals, which include adhesion molecules, MHC-II molecules and cytokines, are necessary to foster the interaction between memory T cells and epidermal cells, that is required to promote cutaneous inflammatory responses. American cutaneous leishmaniasis (ACL) is characterized by a spectrum of immunological manifestations, and is a prototype disease for the study of regulatory mechanisms involved in immune protection against protozoal infection. In the present study, we show that diffuse cutaneous leishmaniasis (DCL) epidermis contains keratinocytes that do not express ICAM-1 and HLA-DR molecules. Langerhans cells (LC) are within normal values or somewhat lower, and a very few cells expressing the HB15 molecule--a new described member of the Ig superfamily--are found in such lesions. Mucocutaneous leishmaniasis (MCL) epithelium shows an increased expression of ICAM-1 and HLA-DR molecules, few HB15+ cells, and an absence of epithelial LC. Localized cutaneous leishmaniasis (LCL) epidermis displays ICAM-1+ keratinocytes organized in patches, a uniform expression of HLA-DR, hyperplasia of LC, and numerous HB15+ cells. In all forms of the disease, infiltrating T cells express more LFA-1 beta than LFA-1 alpha, but LFA-1 beta+ T cells are more abundant in LCL granulomas. In contrast, there are more LFA-1 alpha+ T cells in DCL and MCL than in LCL granulomas. LCL lesions also show the highest numbers of HB15+ cells within the granuloma. These results indicate the importance of adhesion molecules in ACL lesions, and open new possibilities for therapeutic schemes oriented towards the control of cell migration.