Endogenous IL-10 and IFN-γ Production Controls Thymic Cell Proliferation in Mice Acutely Infected by Trypanosoma cruzi |
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Authors: | M D C LEITE DE MORAES P MINOPRIO M DY† M DARDENNE† W SAVINO‡ M HONTEBEYRIE-JOSKOWICZ§ |
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Institution: | Unitéd'Immunoparasitologie, Institut Pasteur, Paris, France;CNRS URA 1461, Hôpital Necker, Paris, France;Department of Immunology, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil;IBBA, La Paz, Bolivie |
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Abstract: | Thymocytes from mice with experimental Trypanosoma cruzi infection respond poorly to Con-A stimulation. However, the proliferative capacity of these cells is not impaired, as demonstrated by the fact that at high doses, exogenous rIL-2 restores thymidine uptake. This finding could be explained either by insufficient IL-2 production or by the appearance of inhibitory factors during T. cruzi infection. This paper shows that in response to Con A, IL-2 production is decreased in the model. Furthermore, the whole profile of cylokine production is modified, with a striking increase in IL-10, IFN-γ, IL-4, IL-5 and IL-6 production. The results indicate that IL-10 it plus IFN-γ are responsible for the decrease in the Con A induced proliferation since a normal proliferative response as well as normal IL-2 production can be restored if both cytokines are neutralized by adding their monoclonal antibodies (MoAbs). Evidence is provided also for an enhanced non-specific cytotoxicity of thymic cells from infected mice that might involve IL-4, IL-5 and IL-6. This is the first study demonstrating an alteration of thymic cell function by T. cruzi infection which results from overstimulation of IL-10 and IFN-γ production. |
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