Lineage relationships, homeostasis, and recall capacities of central– and effector–memory CD8 T cells in vivo

The lineage relationships of central–memory T cells (T_CM) cells and effector–memory T cells (T_EM), as well as their homeostasis and recall capacities, are still controversial. We investigated these issues in a murine model using two complementary approaches: T cell receptor repertoire analysis and adoptive transfer experiments of purified H-Y–specific T_CM and T_EM populations. Repertoire studies showed that approximately two thirds of T_CM and T_EM clones derived from a common naive precursor, whereas the other third was distinct. Both approaches highlighted that T_CM and T_EM had drastically distinct behaviors in vivo, both in the absence of antigen or upon restimulation. T_CM clones were stable in the absence of restimulation and mounted a potent and sustained recall response upon secondary challenge, giving rise to both T_CM and T_EM, although only a fraction of T_CM generated T_EM. In contrast, T_EM persisted for only a short time in the absence of antigen and, although a fraction of them were able to express CD62L, they were unable to mount a proliferative response upon secondary challenge in this model.