Cutting Edge: In the Absence of TGF-β Signaling in T Cells, Fewer CD103+ Regulatory T Cells Develop, but Exuberant IFN-γ Production Renders Mice More Susceptible to Helminth Infection

Multiple factors control susceptibility of C57BL/6 mice to infection with the helminth Heligmosomoides polygyrus, including TGF-beta signaling, which inhibits immunity in vivo. However, mice expressing a T cell-specific dominant-negative TGF-beta receptor II (TGF-beta RII DN) show dampened Th2 immunity and diminished resistance to infection. Interestingly, H. polygyrus-infected TGF-beta RII DN mice show greater frequencies of CD4(+)Foxp3(+)Helios(+) Tregs than infected wild-type mice, but levels of CD103 are greatly reduced on both these cells and on the CD4(+)Foxp3(+)Helios(-) population. Although Th9 and Th17 levels are comparable between infected TGF-beta RII DN and wild-type mice, the former develop exaggerated CD4(+) and CD8(+) T cell IFN-gamma responses. Increased susceptibility conferred by TGF-beta RII DN expression was lost in IFN-gamma-deficient mice, although they remained unable to completely clear infection. Hence, overexpression of IFN-gamma negatively modulates immunity, and the presence of Helios(+) Tregs may maintain susceptibility on the C57BL/6 background. The Journal of Immunology, 2012, 189: 1113-1117.