Figure 1. The anatomic topology of primary and recall T cell responses.

A) During a primary infection, antigen drains from peripheral tissues to draining lymph nodes (LN) which activates naïve T cells specific for that pathogen. Cells expand in lymphoid tissue and migrate out to peripheral tissues to control the infection (which could be referred to as an inside-out immune response). B) At steady-state, memory T cells patrol for reinfection and are heterogeneous, consisting of resident cells that are absent from circulation (T_RM), cells that circulate through blood and lymph, and cells that recirculate though tissue using blood and lymph as conduits. C) Following secondary exposure to antigen, T_RM can proliferate, give rise to an expanded local population of long-lived progeny, redistribute to draining LNs where they may remain resident, and possibly rejoin the circulation. T_RM redistribution from the periphery to LNs and the circulating pool could be referred to as an outside-in immune response. Not pictured: Reactivation of LN circulating memory T cells (i.e., T_CM) recapitulates an inside-out immune response. D) Upon sensing cognate antigen within tissue, T_RM reactivate and alert the local immune system of a reinfection through chemokine and cytokine production. This leads to upregulation of interferon stimulated genes (ISGs), maturation of DCs, activation of T cells and NK cells, adhesion molecule upregulation and recruitment of CD8+ T cells and B cells. T_RM also proliferate and upregulate cytotoxic molecules, likely contributing to killing of infected cells.