Role of IL10Producing Regulatory T Cells in the Persistence of Infection

In the anti-leishmanial response of genetically resistant strains of mice, IL-10 has been suggested to be produced primarily by the infiltrating CD4+ IFN-y-expressing T cells in the lesions.65,66 IL-10 and IFN-y-producing cells constitute approximately 25% of the total IFN-y-expressing population of CD4+ cells in the lesions.66 These cells may correspond to the CD4+ CD25+ regulatory T cells (Tr) observed in cancer, autoimmune diseases, and transplantation.75,76 IL-10 and IFN-y producing cells may differ from Tr cells in that Tr cells produce IL-10 but may exert immunosuppressive effects via IL-10-independent, cell-contact-dependent

Figure 2. Influence of IL-10 on disease outcome following infection with leishmania, as determined in experimental mouse models.

mechanisms. IL-10 and IFN-y producing cells have also been shown to produce TGF-P in certain cases, however, their immunosuppressive properties have been attributed primarily to


Recently, antigen-specific IL-10-producing Tr cells have been detected in a number of infectious diseases. Pathogen-specific CD4+ T cell clones producing both IL-10 and IFN-y have been detected in broncho-alveolar lavages from patients infected with M. tuberculosis.79 These T cell clones produced IL-10 and IFN-y in an antigen-dependent as well as an antigen-independent manner. High frequencies of antigen-specific T cells producing both IL-10 and IFN-y have also been detected in T cell lines derived from patients infected with Borrelia burgdorferi, (Lyme disease),80,81 P. falciparum,8Pneumocystiscarinii,83 HCV,84 Leishmania,85,86 HIV,87 and other retroviral infections.86,88 In addition, both of these cytokines have been detected in the lesions and plasma of patients with Leishmaniasis, suggesting the involvement of IL-10 in clinical persistence and disease reactivation.68 These observations suggest that IL-10 and IFN-y producing cells enriched at the site of infection or lesions may inhibit elimination of the pathogen from the host but at the same time may serve to curtail the harmful inflammatory effects as observed in the IL-10 KO mouse model of L. major infection.

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