Upon primary immunization, antigen-specific T cells proliferate, generating a large number of effector cells that migrate to peripheral tissues to fight pathogens. Some of these primed T cells develop into memory cells, which confer immediate protection as well as the capacity to mount a more rapid and effective secondary immune response. Understanding the multiple facets of immunological memory and its relationship to protection remains a central issue in immunology (1, 2).

Memory T cells have been traditionally viewed as survivors of effector cells that revert to a quiescent state (Figure 1 a). However, memory T cells have been shown to be heterogenous and to comprise at least two subsets, endowed with different migratory capacity and effector function (3–5). Cells of the first subset resemble the effector cells generated in the primary response in that they lack the lymph node–homing receptors L-selectin and CCR7 and express receptors for migration into inflamed tissues. Upon re-encounter with antigen, these “effector memory T cells”(T EM) can rapidly produce IFN-γ or IL-4 or release pre-stored perforin. Cells of the second subset express L-selectin and CCR7 as naive T cells and lack immediate effector function. These “central memory T cells”(T CM) have a low activation threshold and, upon restimulation in secondary lymphoid organs, proliferate and differentiate to effectors (6).