For their survival in the periphery, naive T cells require periodic stimulation with the cytokines IL-7 and IL-15 and with self-antigens presented by self MHC molecules. On priming with its specific antigen, a naive T cell divides and differentiates. Most of the progeny differentiate into relatively short-lived effector cells that have lost expression of the IL-7 receptor (yellow), but some effector cells retain or reexpress the receptor and become long-lived memory T cells. These memory cells can be maintained by IL-7 and IL-15 and are less dependent on contact with self peptide:self MHC complexes for survival compared with naive T cells. However, contact with self antigens may be necessary for some memory T cells to keep up their numbers in the memory pool, but this may vary between different clones and is the subject of ongoing investigation.
11-22 Memory T cells are heterogeneous and include central memory, effector memory, and tissue-resident subsets.
Changes in other cell-surface proteins that occur on memory CD4 T cells after exposure to antigen are significant (see Fig. 11.27). L-selectin (CD62L) is the homing receptor that directs T cells into secondary lymphoid tissues, and it is lost by effector cells and most memory CD4 T cells. CD44 is a receptor for hyaluronic acid and other ligands expressed in peripheral tissues, and it is induced on effector and memory T cells. The change in expression of these two molecules helps memory T cells migrate from the blood into the peripheral tissues rather than migrating directly into lymphoid tissues, as would naive T cells. Different isoforms of CD45, a cell-surface protein tyrosine phosphatase expressed on all hematopoietic cells, are useful in distinguishing naive from effector and memory T cells. The CD45RO isoform is produced because of changes in the alternative splicing of exons that encode the CD45 extracellular domain and identifies effector and memory cells, although it is unclear what functional consequences this change may impose. Some surface receptors, such as CD25, the α subunit of the IL-2 receptor, are expressed on activated effector cells, but not memory cells; however, they can be reexpressed when memory cells are again reactivated by antigen and become effector T cells.