Activated-memory T cells influence naive T cell fate: a noncytotoxic function of human CD8 T cells

T cells are endowed with the capacity to sense their environment including other T cells around them. They do so to set their numbers and activation thresholds. This form of regulation has been well-studied within a given T cell population - i.e., within the naive or memory pool; however, less is known about the cross-talk between T cell subsets. Here, we tested whether memory T cells interact with and influence surrounding naive T cells. We report that human naive CD8 T cells (T-N) undergo phenotypic and transcriptional changes in the presence of autologous activated-memory CD8 T cells (T-Mem). Following in vitro coculture with activated central memory cells (T-CM), -3% of the T-N acquired activation/memory canonical markers (CD45RO and CD95) in an MHC-I dependent-fashion. Using scRNA-seq, we also observed that -3% of the T-N acquired an activated/memory signature, while -84% developed a unique activated transcriptional profile hybrid between naive and activated memory. Pseudotime trajectory analysis provided further evidence that T-N with an activated/memory or hybrid phenotype were derived from T-N. Our data reveal a non-cytotoxic function of T-Mem with potential to activate autologous T-N into the activated/memory pool. These findings may have implications for host-protection and autoimmunity that arises after vaccination, infection or transplantation.

Automated summary

Activated memory T cells can influence the phenotype and transcription of surrounding naive T cells, which may have implications for immune responses following vaccination, infection, or transplantation.