Clustering of the T-cell receptors signals a reorientation of the cytoskeleton that polarizes the effector cell and focuses the release of effector molecules at the site of contact with the target cell. This is illustrated for a cytotoxic T cell in Fig. 9.38. An important intermediary in the effect of T-cell signaling on the cytoskeleton is the Wiskott–Aldrich syndrome protein (WASp), defects in which result in the inability of T cells to become polarized, among other effects, and cause an immune deficiency syndrome for which the protein is named (see Sections 7-19 and 13-6). Activation and recruitment of WASp by T-cell receptor signaling is mediated by the adaptor protein Vav (see Section 7-19). Polarization starts with the local reorganization of the cortical actin cytoskeleton at the site of contact; this in turn leads to the reorientation of the microtubule-organizing center (MTOC), the center from which the microtubule cytoskeleton is produced, and reorientation of the Golgi apparatus (GA), through which most proteins destined for secretion travel. In the cytotoxic T cell, the cytoskeletal reorientation focuses exocytosis of the preformed cytotoxic granules at the site of T-cell contact with its target cell. The polarization of a T cell also focuses the secretion of newly synthesized effector molecules induced by ligation of the T-cell receptor. For example, the secreted cytokine IL-4, which is the principal effector molecule of TH2 cells, is confined and concentrated at the site of contact with the target cell.
Thus, the T-cell receptor controls the delivery of effector signals in three ways: it induces tight binding of effector cells to their target cells to create a narrow space in which effector molecules can be concentrated; it focuses delivery of effector molecules at the site of contact by inducing a reorientation of the secretory apparatus of the effector cell; and it triggers the synthesis and/or release of the effector molecules. All these mechanisms contribute to targeting actions of effector molecules onto the cell bearing specific antigen. Effector T-cell activity is thus highly selective for appropriate target cells, even though effector molecules themselves are not antigen-specific.
9-26 The effector functions of T cells are determined by the array of effector molecules that they produce.
The effector molecules produced by effector T cells fall into two broad classes: cytotoxins, which are stored in specialized cytotoxic granules and released by CD8 cytotoxic T cells (see Fig. 9.38), and cytokines and related membrane-associated proteins, which are synthesized de novo by all effector T cells. Cytotoxins are the principal effector molecules of cytotoxic T cells and are discussed in Section 9-31. Their release in particular must be tightly regulated because they are not specific: they can penetrate the lipid bilayer and trigger apoptosis in any cell. By contrast, CD4 effector T cells act mainly through the production of cytokines and membrane-associated proteins, and their actions are largely restricted to cells bearing MHC class II molecules and expressing receptors for these proteins.
The main effector molecules of T cells are summarized in Fig. 9.39. The cytokines are a diverse group of proteins and we will review them briefly before discussing the T-cell cytokines and their actions. Secreted cytokines and membrane-associated molecules often act in concert to mediate these effects.
9-27 Cytokines can act locally or at a distance.
Cytokines are small soluble proteins secreted by cells that can alter the behavior or properties of the secreting cell itself (autocrine actions) or of another cell (paracrine actions). Cytokines are produced by many cell types in addition to those of the immune system. We have already introduced the families of