Memory T cells are heterogeneous, and both CD4 and CD8 T cells are classified into three major subsets. Each type exhibits a distinct pattern of receptors, for example, for different chemokines and adhesion molecules, and shows different activation characteristics (Fig. 11.30). Central memory T cells (TCM) express the chemokine receptor CCR7, which allows their recirculation to be similar to that of naive T cells and allows them to traffic through the T-cell zones of peripheral lymphoid tissues. Central memory cells are very sensitive to cross-linking of their T-cell receptors and rapidly express CD40 ligand in response; however, they are relatively slower compared with other memory subsets to acquire effector functions such as production of cytokines early after restimulation. Central memory cells primarily migrate from the blood, into the secondary lymphoid organs, then into the lymphatic system and back into the blood, a route very similar to the migration pattern of naive T cells. By contrast, effector memory T cells (TEM) lack the chemokine receptor CCR7, but express high levels of β1 and β2 integrins, and so are specialized for rapidly entering inflamed tissues. They also express receptors for inflammatory chemokines and can rapidly mature into effector T cells and secrete large amounts of IFN-γ, IL-4, and IL-5 early after restimulation. Effector memory T cells migrate from the blood primarily into peripheral nonlymphoid tissues, then through the lymphatic system and finally into secondary lymphoid tissues. There they can reenter the lymphatic system and reach the blood again. In contrast to central and effector memory cells, tissue-resident memory T cells (TRM) comprise a substantial fraction of memory T cells that do not migrate, but rather take up long-term residency in various epithelial sites (Fig. 11.31). Like TEM cells, TRM cells lack CCR7 but express other chemokine receptors (for example, CXCR3, CCR9) that allow migration into peripheral tissues such as the dermis or the lamina propria of the intestine. In these sites, TRM cells induce CD69, which
CD45RO CCR3 CCR5 Effector memory cells lack CCR7 and migrate to tissues CCR7 Central memory cells express CCR7 and remain in lymphoid tissue CD45RO Most effector cells die after a few days Some effector cells may become quiescent memory cells Memory cells derive directly from some effector T cells CD45RO IL-7R˜Effector T cells differentiate, secrete cytokines, and express cytokine receptors IL-4 IL-2 perforin FasL Naive T cell sees antigen T dendritic cell CD45RACCR7
Fig. 11.30 T cells differentiate into central memory and effector memory subsets, which are distinguished by the expression of the chemokine receptor CCR7.
Quiescent memory cells bearing the characteristic CD45RO surface protein can arise from activated effector cells (right half of diagram) or directly from activated naive T cells (left half of diagram). Two types of quiescent memory T cells can derive from the primary T-cell response: central memory cells and effector memory cells. Central memory cells express CCR7 and remain in peripheral lymphoid tissues after restimulation. Memory cells of the other type—effector memory cells—mature rapidly into effector T cells after restimulation, and secrete large amounts of IFN-γ, IL-4, and IL-5. They do not express the receptor CCR7, but express receptors (CCR3 and CCR5) for inflammatory chemokines.
reduces S1PR expression, thereby promoting retention in tissues. TRM cells, particularly CD8 TRM cells, enter and reside within the epithelium. TGF-βproduction by epithelial cells induces TRM cells to express the integrin αE:β7, which binds E-cadherin expressed by epithelium and is required for TRM retention.