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Differentiation of T cells. Naïve CD4-positive T cells that have never experienced an antigen (Th0) are stimulated by an antigen-presenting cell (APC) such as a dendritic cell. The APC presents the antigen on a major histocompatibility complex (MHC) class II molecule to the T-cell receptor (TCR) on a T cell (signal 1). In the presence of co-stimulatory signals (so-called signal 2) provided by CD80 (B7.1) and CD86 (B7.2) on the APC to CD28 on the Th0 cell, the T cell is properly activated. The activated T cell is induced then to differentiate into one or more different fates that depend on the local cytokine milieu. This cytokine milieu is mainly derived from the APC itself and thus the innate immune response (boxed area in figure). In this manner, interleukin-12 (IL12) induces Th1 cells; IL-4 induces Th2 cells; IL-23 induces transforming growth factor β (TGFβ), IL-6 and IL-1 induce Th17 cells; TGFβ, IL-6, and retinoic Source: Chapter 2. Inflammatory Bowel Disease: Immunologic Considerations & Therapeutic Implications, CURRENT Diagnosis & Treatment: acid induce natural (n) T regulatory (Treg) cells; and interferon-α (IFNα) induces T regulatory 1 cells (Tr1). Each T cell is maintained in its differentiated Gastroenterology, Hepatology, & Endoscopy, 2e state by intracellular transcription factors. These include T-bet (Th1), GATA-3 (Th2), RORt (Th17), and FoxP3 (nTreg). The differentiated T cells secrete a Greenberger NJ, Blumberg RS,TBurakoff R. CURRENT & Treatment: Hepatology, Endoscopy, 2e; 2012 characteristicCitation: profile of cytokines (shown above the cells). Cells in red are Diagnosis effector cells, and cells Gastroenterology, in gray are regulatory cells that&inhibit inflammation. Available at: http://mhmedical.com/ Accessed: May 10, 2017 nTreg, natural T regulatory cell (see Figure 2–6). Copyright © 2017 McGraw-Hill Education. All rights reserved