Click on one of the boxes below to see the processes that promote Th1 differentiation and the transcription factors, secreted molecules, and some of the cell surface markers that distinguish a differentiated Th1 cell from the other T helper cell subtypes.
CD4+ T cells play a central role in the adaptive immune response. Following T cell receptor activation and co-stimulation by antigen-presenting cells, naïve CD4+ T cells differentiate into one of several lineages of T helper cell subtypes depending primarily on cytokines present in the extracellular environment. In the presence of IL-27 and IL-12, naïve CD4+ T cells differentiate into T helper type 1 (Th1) cells. Th1 cells are required for host defense against intracellular viral and bacterial pathogens. IL-27 promotes early commitment to the Th1 lineage by activating STAT1 signaling to induce expression of the Th1-specific transcription factor, T-bet, and inhibit expression of the Th2-specific transcription factor, GATA-3. T-bet serves as the master regulator of Th1 differentiation. It promotes expression of both IL-12 R beta 2 and IFN-gamma, the signature cytokine produced by Th1 cells. IL-12 R beta 2 dimerizes with IL-12 R beta 1 to form a functional IL-12 receptor complex. This renders the cells responsive to IL-12, which is critical for Th1 differentiation. IL-12 signaling stimulates STAT4-dependent expression of IFN-gamma and IL-18 R beta. Formation of the IL-18 receptor complex allows IL-18 signaling to further drive IFN-gamma expression through AP-1-dependent transcription. In addition to activation of STAT4, IL-12, along with IFN-gamma, activates STAT1 to maintain T-bet expression and Th1-specific cytokine production.
To learn more, please visit our Th1 Cells Research Area.