Figure 1.

A schematic of Il2^−/− mutant gene effect on skin and lung inflammation in Sf mice: (A) The dendritic cells (DC) that travel from skin and lungs and carry Ag will go to the draining lymph nodes where they will activate in an unabated manner the Ag-specific Th-cells in the absence of T_reg. IL-4-producing Th2 response is also expanded based on Th-subset cytokine mRNA responses. In addition, a large panel of trafficking receptor genes for skin and lungs is also induced, allowing both Th1 and Th2 cells to enter the skin and lungs upon receiving chemokines and chemo-attractants from macrophages, mast cells, etc. Once entering the organs, they will be activated by local APC bearing the specific Ag. Again, the inflammation will be unabated in the absence of T_reg. (B) In Sf.Il2^−/− mice, although the reactions in the draining LN and their Th-subset cytokine mRNA response seem similar to or just slightly lower than that in Sf mice, the trafficking receptor genes for skin and lungs are not expanded without IL-2. Th1 and Th2 cells could not enter the skin and lungs to induce inflammation. It is important to note that the development of Th1 and Th2 subsets do not depend on IL-2. However, our ex vivo analysis of the subsets indicates that Th2 cells of Sf.Il2^−/− LN T-cells could not be effectively activated whereas Th1 cells were strongly stimulated based on their Th cytokine production. It is also noted that strong inflammation was observed in Sf.Il4^−/− and Sf.STAT-6^−/− mice, indicating that IL-4⁺ Th2 cells were not required for Sf mice to develop skin and lung inflammation.