Regulatory T cells limit unconventional memory to preserve the capacity to mount protective CD8 memory responses to pathogens

Abstract

Abstract Immunological memory exists so that following infection, an expanded population of pathogen-specific lymphocytes can rapidly and efficiently control infection in the case of re-exposure. However, in the case of CD8+ T lymphocytes, a population of unconventional CD44+CD122+ virtual memory T cells (TVM) has been described that possesses many, though not all, features of “true memory” T cells, without the requirement of first encountering cognate antigen. Here, we demonstrate a novel role for regulatory T cell-mediated restraint of TVM through limiting IL-15 trans-presentation by CD11b+ dendritic cells. Further, we show that keeping TVM in check ensures development of functional, antigen-specific “true” memory phenotype CD8 T cells that can assist in pathogen control upon re-exposure.