CD45RB Status of CD8+ T Cell Memory Defines T Cell Receptor Affinity and Persistence

The identity of CD45 isoforms on the T cell surface changes following the activation of naive T cells and impacts intracellular signaling. In this study, we find that the anti-viral memory CD8(+) T pool is unexpectedly comprised of both CD45RB(hi) and CD45RB(lo) populations. Relative to CD45RB(lo) memory T cells, CD45RB(hi) memory T cells have lower affinity and display greater clonal diversity, as well as a persistent CD27(hi) phenotype. The CD45RB(hi) memory population displays a homeostatic survival advantage in vivo relative to CD45RB(lo) memory, and long-lived high-affinity cells that persisted long term convert from CD45RB(lo) to CD45RB(hi). Human CD45RO(+) memory is comprised of both CD45RB(hi) and CD45RB(lo) populations with distinct phenotypes, and antigen-specific memory to two viruses is predominantly CD45RB(hi). These data demonstrate that CD45RB status is distinct from the conventional central/effector T cell memory classification and has potential utility for monitoring and characterizing pathogen-specific CD8(+) T cell responses.