TYPES of T.CELL and Th1 cells.

Helper T (Th) Cells

CD4⁺ T cells play an integral role in adaptive immune responses. When a pathogen is detected, information is communicated to T cells through antigen presentation. Following activation, naive CD4⁺ T cells differentiate into one of several lineages of T helper cells (Th1, Th2, Th9, Th17, or Th22), depending primarily on the antigen, the strength of the TCR signal, and the cytokines present in the surrounding extracellular environment. Differentiation of each T cell subset is associated with the expression of specific transcription factors followed by secretion of a defined array of cytokines that orchestrate a directed response to the antigen. The actions of T helper cells are balanced by regulatory T (Treg) cells, a subpopulation that specializes in suppression of T cell-mediated immune responses. Failure to activate an appropriate T cell response can lead to chronic infection, while exaggerated T cell responses can cause excessive tissue damage and are associated with inflammatory and autoimmune diseases.

        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.

Th1 Differentiation Pathway

Overview of Th1 Differentiation

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