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.

JAVIER VOGT; CATALINA DIRNEY ALBA SOTO; MARIANA PAULA MINCZ; GERARDO A. MIRKIN

MICROBES AND INFECTION

Institut Pasteur

Año: 2008 vol. 10 p. 781 - 790

1286-4579

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-ã 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-ã, no IL-4 production, and higher levels of IL-10 secretion under the same conditions. Our results show that T. cruzi-specific IFN-ã- 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-ã secretion might subside due to the overt secretion of IL-10, of which TCRBV9+ T cells represent a significant source.