Development of naive Th cells into Th1 and Th2 effector populations requires coordinated expression of a complex set of genes. In this study, we have identified a novel four-transmembrane domain protein, Chandra, that is differentially expressed in Th1 cells. Chandra expression is observed in STAT4- and IFN-gamma-deficient mice, indicating that Chandra is not an IL-12- or IFN-gamma-responsive gene. Interestingly, Chandra mRNA is detected in anti-CD3-activated T cells from STAT6-deficient mice in the absence of any differentiation conditions. Furthermore, neutralization of IL-4 signaling is sufficient to induce transcription of Chandra in anti-CD3-activated T cells from wild-type mice, demonstrating that STAT6 signaling is required to repress Chandra expression in activated T cells and Th2 subsets. This is the first demonstration of a differentially expressed four-transmembrane domain protein in Th1 cells.