Many lymphocytes and other cells in lymphoid tissue produce cytokines. These small secreted proteins control lymphocyte activity by binding to specific cytokine receptors on the surface of a lymphocyte and initiating a transcriptional program that allows the lymphocyte to either proliferate or differentiate into an effector cell ready to exert cytotoxic (cytotoxic T cells), helper (helper T cells), or antibody-secreting activity (B cells). Cytokines that are produced by or act primarily on leukocytes are called interleukins; at least 35 interleukins have been recognized and molecularly characterized. Each type of interleukin receptor has some structural similarity to the others; those interleukins whose structures are most closely related can be recognized by their cognate receptors. The interleukin-2 receptor is particularly well characterized. Interleukin 2 (IL-2), a T-cell growth factor, is one of the first cytokines produced when T cells are stimulated. IL-2 acts as an autocrine (self-acting) and paracrine (acting on neighboring cells) growth factor and drives clonal expansion of activated T cells.

Interleukin 4 (IL-4), which is produced by helper T cells, induces activated B cells to proliferate and to undergo class-switch recombination and somatic hypermutation. Interleukin 7 (IL-7), produced by stromal cells in the bone marrow, is essential for development of T and B cells. Both IL-7 and IL-15 play a role in the maintenance of memory cells, which are antigen-experienced T cells that may be called upon when re-exposure to antigen occurs. These memory cells then rapidly proliferate and deal with the re-invading pathogens. The receptors for IL-2, IL-4, IL-7, and IL-15 all rely on a common subunit for signal transduction, the common γ chain (γ_c), with α (IL-2, IL-15) and β subunits (IL-2, IL-4, IL-7, IL-15) providing ligand specificity. Genetic defects in the γ_c result in nearly complete failure of lymphocyte development, illustrating the importance of these cytokines not only during the effector phase of an immune response, but also in the course of lymphocyte development, where IL-7 in particular plays a key role.

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The mechanism of signal transduction by cytokine receptors through the JAK/STAT pathway is described in Chapter 16 (reviewed in Figure 16-1). Among the many genes under the control of interleukins and the STAT pathway are those that encode suppressors of cytokine signaling, or SOCS proteins. These proteins, which are themselves induced by cytokines, bind to the activated form of JAKs and target them for proteasomal degradation (see Figure 16-13b).