Migration, maintenance and recall of memory T cells in peripheral tissues

Key Points Memory T cells are established at both lymphoid and peripheral sites following the clearance of an invading pathogen. However, memory T-cell transfer and parabiosis studies have shown that the migration of circulating memory T cells into some peripheral tissues, such as the skin, gut, lung airways and brain, is highly restricted. The ability of memory T cells to selectively migrate into different peripheral tissues is controlled by the expression of different combinations of adhesion molecules and chemokine receptors. The ability of T cells to express these specific combinations of surface molecules is 'imprinted' during initial antigen priming and depends on molecular cues that are governed by the lymph node microenvironment. Memory T cells in peripheral tissues are more resistant to apoptosis than their systemic counterparts, which allows them to survive despite the close proximity to the external environment. Although the mechanism has yet to be identified, this increased resistance to apoptosis is gained when circulating memory T cells enter peripheral tissues. Peripheral memory T cells are mostly of the CD62L − CCR7 − (CC chemokine receptor 7) effector memory T (T EM )-cell phenotype. As the pathogen-specific memory T-cell pool gradually converts to a CD62L + CCR7 + central memory T (T CM )-cell phenotype, there are fewer pathogen-specific cells that are capable of migrating into peripheral tissues. Following clearance of an influenza virus infection, antigen persists in the draining lymph nodes of the lung for several months. This residual antigen contributes to the large number of antigen-specific memory T cells that are present in the lung airways for several months after infection, and the elimination of these antigen depots coincides with the gradual decline in memory T-cell numbers in the lung airways. During a secondary infection, memory T cells in peripheral tissues can be directly activated by pro-inflammatory cytokines to induce effector functions and can interact with antigen-bearing dendritic cells to generate a localized secondary effector T-cell response outside of the draining lymphoid tissue. Together, these actions result in a rapid response at the site of infection that can limit pathogen replication prior to the arrival of secondary effector T cells from the lymph nodes. Vaccination with live viral vectors has proven successful at generating mucosal T-cell memory because effector T cells that had trafficked to antigen-fre