Figure 2

CD4+ T helper subsets. CD4+ T cells can differentiate into different subsets depending on the cytokine milieu present during T cell activation. T_H1 cells, activated in the presence of IL-12 and IL-18 produced by activated DCs, make IFNγ, which is important in activating macrophages to kill intracellular bacteria, such as M. tuberculosis. IL-4 made by T_H2 cells activates macrophages to expel parasites (the cellular source of the IL-4 that promotes T_H2 development is currently poorly defined). T follicular (Tfh) cells can make the canonical cytokines that T_H1 or T_H2 cells produce, but they also make IL-21 and express cell-surface molecules, such as CD40 ligand and inducible T cell co-simulator (ICOS), that are required for effective B cell responses and production of high-affinity, class-switched antibodies. The more recently described T_H17 cells can produce IL-17 and IL-22 and are generated in the presence of IL-6 and TGFβ. IL-17 and IL-22 are important for promoting the influx of neutrophils to inflamed sites and the production of antimicrobial peptides, respectively. T_H17 cells are thought to be important in defense against extracellular bacteria and fungi. Activated T cells can also differentiate into regulatory T cells (Tregs) in the presence of TGFβ and/or retinoic acid (RA). These cells can inhibit and control immune responses to prevent excessive inflammation through cell-surface molecules (such as CTLA-4) or cytokines, such as IL-10.