CD69 guides CD4+ T cells to the seat of memory.

I mmunologists’ views on the cellular basis of immune memory have undergone substantial modifications over the last decade, with new findings advancing the field from mostly descriptive studies of their presumptive phenotypes to those that allow the features distinguishing memory cells from short-lived effectors to be known and understood (1). Although such studies have helped to define the functional qualities of memory cells, more recent attention has been paid to the “where” of immune memory through comparison of the number and quality of memory T and B cells in various anatomical sites. These studies have produced the rather surprising finding that, rather than residing in the secondary lymphoid organs where most immune responses are initiated, many types of memory cells have been shown to preferentially accumulate in the bone marrow (BM), a site more often associated with hematopoiesis (2). As expected, such observations immediately lead back to the question of “how” this process occurs in terms of homing behavior and retention within specialized niches. In PNAS, Shinoda et al. provide a compelling answer for CD4 memory T cells by showing that expression of the activation marker CD69 is critical for the persistence of CD4 T cell memory in the bone marrow environment (3).