cytokines and their receptors that are important in innate and adaptive immunity in Chapters 3 and 7 (see Sections 3-15 and 7-1). Here we are concerned with cytokines that mediate the effector functions of T cells. Many cytokines produced by T cells are given the name interleukin (IL) followed by a number. The cytokines produced by T cells are shown in Fig. 9.40, and a more comprehensive list of cytokines of immunological interest is in Appendix III. Although many cytokines can have diverse biological effects when tested in vitro, targeted disruption of the genes for cytokines and cytokine receptors in mice (see Appendix I, Section A-35) has helped to clarify their physiological roles.
Binding of the T-cell receptor orchestrates the polarized release of cytokines so that they are concentrated at the site of contact with the target cell (see Section 9-25). Furthermore, most of the soluble cytokines have local actions that synergize with those of the membrane-bound effector molecules. The effect of all these molecules is therefore combinatorial, and, because the membrane-bound effectors can bind only to receptors on an interacting cell, this is another mechanism by which selective effects of cytokines are focused on the target cell. The effects of some cytokines are further confined to target cells by tight regulation of their synthesis: the synthesis of IL-2, IL-4, and IFN-γ, for example, is controlled by mRNA instability (see Section 9-16), so that their secretion by T cells does not continue after the interaction with a target cell has ended.
Some cytokines have distant effects. IL-3 and GM-CSF (see Fig. 9.39) are released by TH1, TH2, and TH17 cells and act on bone marrow cells to stimulate the production of macrophages and granulocytes, which are important innate effector cells in both antibodyand T-cell-mediated immunity. IL-3 and GM-CSF also stimulate the production of dendritic cells from bone marrow precursors. IL-17A and IL-17F produced by TH17 cells act primarily on stromal cells, activating them to produce G-CSF, which enhances production
Fig. 9.40 The nomenclature and functions of well-defined many effects through what is called a ‘cytokine network.’ ↑ increase; T-cell cytokines. each cytokine has multiple activities on different ↓, decrease; CTL, cytotoxic lymphocyte; nK cells, natural killer cells; cell types. Major activities of effector cytokines are highlighted in CsF, colony-stimulating factor; IBd, inflammatory bowel disease; no, red. The mixture of cytokines secreted by a given cell type produces nitric oxide.
of neutrophils by the bone marrow. TH2 cells produce IL-5, which stimulates bone marrow production of eosinophils. Whether a given cytokine effect is local or more distant is likely to reflect the amounts released, the degree to which this release is focused on the target cell, and the stability of the cytokine in vivo.
9-28 T cells express several TNF-family cytokines as trimeric proteins that are usually associated with the cell surface.