Regulation of ST2L expression on T helper (Th) type 2 cells

T1/ST2L, an IL-1 receptor homologue, is selectively expressed on murine Th2 cells and specific anti-ST2L antibodies can profoundly modulate the Th1/Th 2 balance in vivo. Naive CD4(+) T cells do not express ST2L but do so on ac tivation with specific antigen in the presence of IL-4 or when stimulated w ith low doses of antigen in the absence of exogenously added IL-4. Similarl y enhanced ST2L expression occurred after stimulation of Th2 cells with ant igen or the mitogen ConA in the presence of APC. Restimulation of Th2 cells in the presence of IFN-gamma led to a decreased expression of ST2L to belo w basal levels. Conversely, Th2 cells cultured with IL-4 led to increased S T2L expression. The reduced expression of ST2L in response to high doses of antigen is also reversed by the neutralization of IFN-gamma. Using an ST2L promoter/luciferase reporter gene construct, we show that the distal but n ot proximal ST2L promoter is responsible for specific gene expression in Th 2 cells. IL-4 enhances, whereas IFN-gamma suppresses ST2L expression via di rect modulation of the distal promoter of the ST2L gene. These data provide a mechanistic explanation for the selective expression of ST2L on Th2 cell s.