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.