RESUMO
The host response to infection appears to be regulated by specific patterns of local cytokine production. In the mouse, resistance to many pathogens including Leishmania is associated with a TH1 cytokine profile, IL-2 and IFN-gamma; whereas susceptibility to infection is associated with production of TH2 cytokines, IL-4, IL-5, and IL-10. To determine the cytokine patterns of the local immune response to Leishmania infection in humans, we used the polymerase chain reaction to compare cytokine mRNAs in biopsy specimens of American cutaneous leishmaniasis. In localized cutaneous leishmaniasis and the Montenegro delayed-type hypersensitivity reaction, type 1 cytokine mRNAs such as IL-2, IFN-gamma, and lymphotoxin were relatively predominant. In the chronic and destructive mucocutaneous form of leishmaniasis, there was a mixture of type 1 and type 2 cytokines, with a striking abundance of IL-4 mRNA in lesions. These results suggest that clinical course of infection with Leishmania braziliensis in man is associated with specific local patterns of cytokine production.
Assuntos
Citocinas/metabolismo , Leishmaniose/etiologia , Adolescente , Adulto , Idoso , Sequência de Bases , Biópsia , Criança , Feminino , Humanos , Leishmaniose/metabolismo , Leishmaniose/patologia , Leishmaniose Cutânea/patologia , Linfocinas/genética , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , RNA Mensageiro/análise , Pele/química , Pele/patologiaRESUMO
American cutaneous leishmaniasis is a disease of skin and mucous membranes in which T lymphocytes reactive to Leishmania (Viannia) braziliensis are thought to contribute to protective immunity. To characterize the nature of the T cell inflammatory infiltrate in American cutaneous leishmaniasis lesions, immunohistochemistry with mAb that define T cell subpopulations and in situ hybridization to detect mRNA coding for IFN-gamma were performed. In both localized cutaneous (LCL) and mucocutaneous (MCL) lesions, we observed a predominance of T memory (CD4+CD45RO+) as compared to T naive cells (CD+CD45RA+). The percentages of cells containing IFN-gamma mRNA were equivalent in both LCL and MCL lesions. T cells were extracted from LCL and MCL lesions and analysis indicated that T cells from both lesions had been stimulated by L. (V.) braziliensis in vivo and gave equivalent proliferative responses in vitro. The present data suggest that T memory cells, which are likely to elaborate IFN-gamma, are components of DTH response to L. (V.) braziliensis and participate in the pathogenesis of both LCL and MCL lesions.