Endogenous IL-10 and IFN-gamma production controls thymic cell proliferation in mice acutely infected by Trypanosoma cruzi.
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 cytokine production is modified, with a striking increase in IL-10, IFN-gamma, IL-4, IL-5 and IL-6 production. The results indicate that IL-10 plus IFN-gamma 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-gamma production.
Leite de Moraes
M D
MD
Unité d'Immunoparasitologie, Institut Pasteur, Paris, France.
Minoprio
P
P
Dy
M
M
Dardenne
M
M
Savino
W
W
Hontebeyrie-Joskowicz
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology*; D003208:Concanavalin A / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D003208:Concanavalin A; D016753:Interleukin-10; D007371:Interferon-gamma