Homeostatic cytokines orchestrate the segregation of CD4 and CD8 memory T-cell reservoirs in mice.

Memory T cells (T(M)s) have been detected in many tissues but their quantitative distribution remains largely undefined. We show that in mice there is a remarkably biased accumulation of long-term CD4 T(M)s into mucosal sites (mainly gut, especially Peyer patches), and CD8 T(M)s into lymph nodes and spleen (in particular, peripheral lymph nodes [PLNs]). This distinction correlates with their differentiated expression of PLN- and gut-homing markers. CD8 and CD4 T(M)s selectively require the expression of PLN-homing marker CCR7 or gut-homing marker α4β7 for maintenance. PLNs and gut supply CD8 and CD4 T(M)s with their individually favored homeostatic cytokine, IL-15, or IL-7. Cytokine stimulation in turn regulates the different gut-homing marker expression on CD4 and CD8 T(M)s. IL-15 plays a major role in vivo regulating CD8 T(M)s homing to PLNs. Thus, the reservoir segregation of CD4 and CD8 T(M)s meets their individual needs for homeostatic cytokines and is under feedback control of cytokine stimulation.