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.

Functional subsets of human T cells were delineated by analyzing patterns of lymphokines produced by clones from individuals with leprosy and by T cell clones of known function. CD4 clones from individuals with strong cell-mediated immunity produced predominantly interferon-gamma, whereas those clones that enhanced antibody formation produced interleukin-4. CD8 cytotoxic T cells secreted interferon-gamma. Interleukin-4 was produced by CD8 T suppressor clones from immunologically unresponsive individuals with leprosy and was found to be necessary for suppression in vitro. Both the classic reciprocal relation between antibody formation and cell-mediated immunity and resistance or susceptibility to certain infections may be explained by T cell subsets differing in patterns of lymphokine production.

The immunological mechanisms required to engender resistance have been defined in few infectious diseases of man, and the role of specific cytokines is unclear. Leprosy presents clinically as a spectrum in which resistance correlates with cell-mediated immunity to the pathogen. To assess in situ cytokine patterns, messenger RNA extracted from leprosy skin biopsy specimens was amplified by the polymerase chain reaction with 14 cytokine-specific primers. In lesions of the resistant form of the disease, messenger RNAs coding for interleukin-2 and interferon-gamma were most evident. In contrast, messenger RNAs for interleukin-4, interleukin-5, and interleukin-10 predominated in the multibacillary form. Thus, resistance and susceptibility were correlated with distinct patterns of cytokine production.

Delayed-type hypersensitivity (DTH) is the standard measure of T-cell responsiveness to infectious organisms. For leprosy, the Mitsuda reaction, a local immune response to cutaneous challenge with Mycobacterium leprae, is considered to represent a measure of DTH against the pathogen. We analyzed the * Corresponding author.

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