Impaired Trypanosoma cruzi-specific IFN-gamma secretion by T cells bearing the BV9 T-cell receptor is associated with local IL-10 production in non-lymphoid tissues of chronically infected mice.
The role of non-lymphoid tissue T cells expressing the BV9 family T-cell receptor (TCRBV9) was studied in mice chronically infected with the Trypanosoma cruzi. Heart and skeletal muscles had higher frequencies and ratios of CD8+ TCRBV9+ to CD4+ TCRBV9+ T cells than lymph nodes. Also, homing experiments of CFSE-labeled T cells showed preferential homing of TCRBV9+ T cells to heart tissue. In vitro proliferation assays showed higher [3H]thymidine uptake by non-lymphoid tissue TCRBV9+ T cells than lymph node TCRBV9+ T cells co-cultured with antigen-presenting cells (APC), in response to T. cruzi amastigote antigens (TcAg). Lymph node TCRBV9+ T cells secreted IFN-gamma and IL-10, but not IL-4, upon stimulation with TcAg in the presence of APC. Moreover, non-lymphoid tissue-derived TCRBV9+ T cells showed impairment of IFN-gamma, no IL-4 production, and higher levels of IL-10 secretion under the same conditions. Our results show that T. cruzi-specific IFN-gamma- and IL-10-producing TCR BV9+ T cells develop in the mouse lymph nodes during chronic infection with T. cruzi. Upon homing to non-lymphoid parasitized tissues, IFN-gamma secretion might subside due to the overt secretion of IL-10, of which TCRBV9+ T cells represent a significant source.
Departamento de Microbiología, Parasitología e Inmunología. Facultad de Medicina, Universidad de Buenos Aires. Paraguay 2155, Buenos Aires, Argentina.
Javier
J
Vogt
Catalina Dirney
CD
Alba Soto
Mariana Paula
MP
Mincz
Gerardo Ariel
GA
Mirkin
D000818:Animals; D049109:Cell Proliferation; D014355:Chagas Disease / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000276:immunology*; D015847:Interleukin-4 / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018482:Muscle, Skeletal / Q000276:immunology; D009206:Myocardium / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis*; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma