Tyk2 signaling plays a critical role in the development of T cytotoxic 1 responses following chronic rBCG-OVA infections in mice
10.3760/cma.j.issn.0254-5101.2011.01.011
- VernacularTitle:Tyk2信号传导在表达OVA的重组卡介菌(rBCG-OVA)所致慢性胞内细菌感染小鼠模型的CD8+Tc1反应中的作用
- Author:
Wei LI
- Publication Type:Journal Article
- Keywords:
Tyrosine kinase 2;
Mice;
rBCG-OVA;
CD8+ T cell
- From:
Chinese Journal of Microbiology and Immunology
2011;31(1):41-46
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate potential roles of tyrosine kinase 2 (Tyk2) in the generation and maintenance of Ag-specific CD8+ T cells. Methods We followed the fate of OVA-specific CD8 + T cells in Tyk2-deficient ( Tyk2 -/- ) mice after infection with recombinant OVA-expressing BCG ( rBCGOVA ). Because the immunostimulatory BCG-derived peptides recognized by CD8 + T cells have not been defined, and the OVA is definite peptide for specific CD8 + T cells that has been accepted widely, therefore we examine the kinetics of the OVA-Ag-specific CD8 + T cell response after rBCG-OVA infection in mice.Tyk2-/- and wild type(Tyk2+/+ ) mice were inoculated with rBCG-OVA by intra-trachea( i. t. ), after the examination of bacterial growth in the lung and spleen, the population of CD8 + T cells were detected by FACS analysis, the epitope-specific CD8 + T cells were followed with tetrameric H-2Kb molecule folding with OVA257 264 peptide, and the kinetics of Ag-specific CD8 + Tc1 cells were detected by intracellular IFN-γ production in response to OVA257-264 peptide by cytokine FACS analysis. Results After rBCG-OVA challenge,the bacteria number in spleen and lung of Tyk2 -/- mice were significantly larger than those in Tyk2 +/+ mice on days 14, 21 and 49. Almost as same as that in Tyk2+/+ mice, the size of epitope-specific CD8+ T cella with OVA257-264/Kb-tetramer-positive and the CD8 +Tc1 (T eytotoxic 1 )cells positive for intracellular IFN-γ could proliferate to its peak on day 21, then contract and maintain to the memory phase in spleen and lung of Tyk2-/- mice, but the population of CD8+ T cells in spleen and lung of Tyk2 -/- mice were significantly smaller than those in Tyk2+/+ mice on days 21 and 49, the number of epitope-specific CD8+ T cells in spleen and lung of Tyk2 -/- mice were significantly decreased and the frequency of CD8 + Tc1 cells in spleen and lung of Tyk2 -/- mice significantly reduced on day 21,49 and 70 after rBCG-OVA infection. So correspond with the larger number of bacteria in Tyk2-/- mice than those in Tyk2 +/+ mice, the expansion of OVA257-264-specific CD8 + T cells and CD8+ Tc1 response were attenuated in Tyk2 -/- mice following rBCG-OVA infection. Conclusion These results suggest that the lack of Tyk2 signaling impairs the proliferation and difference of effector CD8 + T cell to rBCG-OVA infection and at least, is partly responsible for the susceptible to the rBCG-OVA infection.
