Memory T-cell trafficking: new directions for busy commuters

Abstract

The immune system is unique in representing a network of interacting cells of enormous complexity and yet being based on single cells travelling around the body. The development of effective and regulated immunity relies upon co-ordinated migration of each cellular component, which is regulated by diverse signals provided by the tissue. Co-ordinated migration is particularly relevant to the recirculation of primed T cells, which, while performing continuous immune surveillance, need to promptly localize to antigenic sites, reside for a time sufficient to carry out their effector function and then efficiently leave the tissue to avoid bystander damage. Recent advances that have helped to clarify a number of key molecular mechanisms underlying the complexity and efficiency of memory T-cell trafficking, including antigen-dependent T-cell trafficking, the regulation of T-cell motility by costimulatory molecules, T-cell migration out of target tissue and fugetaxis, are reviewed in this article.

Figure 1

Migratory events in memory T cell trafficking. (a) After generation in the thymus, naïve T cells (TNaive) emigrate to the blood circulation and migrate into lymph nodes (LN) by utilizing the lymphoid tissue homing receptors L-selectin and CCR7 (1). Here, T cells become activated (TM) by antigen-presenting dendritic cells (DC) and acquire homing receptors (2). CD28 signals promote migration of primed T cells to non-lymphoid target tissue. CTLA-4-mediated signals inhibit the migration of primed specific T cells to antigenic sites, and their interactions with antigen presenting cells (APCs). Successfully activated T cells leave LNs via sphingosin receptor-dependent mechanisms (3). (b) Primed T cells migrate to non-lymphoid tissue (4, 5). In conjunction with homing receptors, T-cell receptor (TCR) engagement by endothelium and tissue resident APCs promotes specific T cell recruitment and retention. Memory T cells leave target tissue by CCR7-mediated mechanisms and/or fugetaxis (6). Some memory T cells can return to lymphoid tissue (7). (c) At the end of an immune response, memory T cells can either continue recirculating, or return in niches (8): memory T cells can reside in the spleen in chronic antigen persistence, or they can locate to the bone marrow following acute but transient antigen challenge. MHC, major histocompatibility complex; HEV, high endothelial venules; T_CM, central memory T cells; T_EFF, effector T cells.