Th1 Cells

T helper type 1 (Th1) cells are a lineage of CD4+ effector T cell that promotes cell-mediated immune responses and is required for host defense against intracellular viral and bacterial pathogens. Th1 cells secrete IFN-gamma, IL-2, IL-10, and TNF-alpha/beta. These cytokines promote macrophage activation, nitric oxide production, and cytotoxic T lymphocyte proliferation, leading to the phagocytosis and destruction of microbial pathogens. In addition to the cytokines secreted by Th1 cells, the expression of specific cell surface receptors, including IL-12 R beta 2, IL-27 R alpha/WSX-1, IFN-gamma R2, CCR5, and CXCR3, can be used to distinguish Th1 cells from other T cell subtypes. Th1 cell differentiation and expansion are driven by cytokines that signal through a subset of these receptors, including IL-27, IL-12, and IFN-gamma. IL-27 signaling in naive CD4+ T cells induces STAT1-dependent expression of the Th1-specific transcription factor, T-bet, which promotes expression of IFN-gamma and IL-12 R beta 2. IL-12 R beta 2 heterodimerizes with IL-12 R beta 1 to form a functional IL-12 receptor complex that then stimulates STAT4-dependent IFN-gamma production and Th1 differentiation. Although Th1 cells are critical for the clearance of intracellular pathogens, exaggerated Th1 responses have been found to be associated with autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and type 1 diabetes.