Fig. 9.30 Subsets of CD4 effector T cells are specialized to provide help to different target cells for the eradication of different classes of pathogens. unlike Cd8 T cells, which act directly on infected target cells to eliminate pathogens, Cd4 T cells typically enhance the effector functions of other cells that eradicate pathogens—whether cells of the innate immune system, or, in the case of TFh cells, antigen-specific B cells. Th1 cells (first panels) produce cytokines, such as IFn-γ, which activate macrophages, enabling them to destroy intracellular microorganisms more efficiently. Th2 cells (second panels) produce cytokines that recruit and activate eosinophils (IL-5) and mast cells and basophils (IL-4), and promote enhanced barrier immunity at mucosal surfaces (IL-13) to eradicate helminths. Th17 cells (third panels) secrete IL-17-family cytokines that induce local epithelial and stromal cells to produce chemokines that recruit neutrophils to sites of infection. Th17 cells also produce IL-22, which along with IL-17 can activate epithelial cells at the barrier site to produce antimicrobial peptides that kill bacteria. TFh cells (fourth panels) form cognate interactions with naive B cells through linked recognition of antigen and traffic to B-cell follicles, where they promote the germinal center response. TFh cells produce cytokines characteristic of other subsets and participate in type 1, 2, and 3 responses that are recruited against different types of pathogens. TFh cells producing IFn-γ activate B cells to produce strongly opsonizing antibodies belonging to certain IgG subclasses (IgG1 and IgG3 in humans, and their homologs, IgG2a and IgG2b, in the mouse) in type 1 responses. Those TFh cells producing IL-4 drive B cells to differentiate and produce immunoglobulin Ige, which arms mast cells and basophils for granule release in type 2 responses. TFh cells that produce IL-17 appear to be important for generating opsonizing antibodies directed against extracellular pathogens in the context of type 3/Th17 immunity. regulatory T cells (right panels) generally suppress T-cell and innate immune cell activity and help prevent the development of autoimmunity during immune responses.
we shall discuss further in Chapter 11, the functional features of these T-cell subsets parallel in many ways those of innate lymphoid cells (ILCs), which, although lacking antigenic receptors, produce many of the same patterns of effector cytokines or cytotoxins.
The first CD4 T-cell subsets to be distinguished were the TH1 and TH2 subsets, hence their names. TH1 cells are characterized by the production of IFN-γ, whereas TH2 cells are characterized by the production of IL-4, IL-5, and IL-13. TH17 cells are so named because they produce the cytokines IL-17A and IL-17F; they also produce IL-22. TFH cells develop in concert with TH1, TH2, or TH17 cells to help B cells generate class-switched immunoglobulins of different isotypes, which are targeted to different innate immune effector cells by the array of Fc receptors they display. Treg cells have immunoregulatory function and promote tolerance to, rather than clearance of, the antigens they recognize.