T-cell effector functions involve the interaction of an effector T cell with a target cell displaying specific antigen. Effector proteins expressed by the T cell, whether cell-associated (for example, CD40L) or secreted (for example, cytokines), are focused on the target by mechanisms that are activated by antigen recognition. The focusing mechanism is common to all types of effector T cells, whereas their effector actions depend on the type of effector T cell that is engaged.
9-24 Effector T-cell interactions with target cells are initiated by antigen-nonspecific cell-adhesion molecules.
Once an effector T cell has completed its differentiation in the lymphoid tissue, it must find target cells that are displaying the peptide:MHC complex that it recognizes. TFH cells encounter their B-cell targets without leaving the lymphoid tissue. However, most other effector T cells emigrate from their site of activation in lymphoid tissues and enter the blood, either directly if primed by antigen in the spleen or via the efferent lymphatics and thoracic duct if primed in lymph nodes. Because of the cell-surface changes that have occurred during their differentiation, effector T cells can now migrate into tissues, particularly at sites of infection. They are guided to these sites by changes in the adhesion molecules expressed on the endothelium of the local blood vessels as a result of infection, and by local chemotactic factors, as will be discussed further in Chapter 11.
The initial binding of an effector T cell to its target, like that of a naive T cell to an antigen-presenting cell, is an antigen-nonspecific interaction mediated by LFA-1 and CD2. The levels of LFA-1 and of CD2 are twoto fourfold higher on effector T cells than on naive T cells, and so effector T cells can bind efficiently to target cells that have less ICAM and CD58 on their surface than do antigen-presenting cells. This interaction is transient unless recognition of antigen on the target cell by the T-cell receptor triggers an increase in the affinity of the T-cell’s LFA-1 for its ligands. The T cell then binds more tightly to its target and remains bound long enough to release its effector molecules. Effector CD4 T cells, which activate macrophages or induce B cells to secrete antibody, have to switch on new genes and synthesize new proteins to carry out their effector actions and so must maintain contact with their targets for relatively long periods. Cytotoxic T cells, by contrast, can be observed under the microscope attaching to and dissociating from successive targets relatively rapidly as they kill them (Fig. 9.36). Killing of the target, or some local change in the T cell, allows the effector T cell to detach and address new targets. How CD4 effector T cells disengage from their antigen-negative targets is not known, although evidence suggests that CD4 binding to MHC class II molecules without engagement of the T-cell receptor provides a signal for the cell to detach.
their targets to regulate signaling and to direct the release of effector molecules.
When binding to their specific antigenic peptide:self MHC complexes or to self peptide:self MHC complexes, the T-cell receptors and their associated co-receptors cluster at the site of cell–cell contact, forming what is called the supramolecular activation complex (SMAC) or the immunological synapse. Other cell-surface molecules also cluster here. For example, the