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

Abstract

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 naïve 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 naïve T cells. We report that human naïve CD8 T cells (TN) undergo phenotypic and transcriptional changes in the presence of autologous activated-memory CD8 T cells (TMem). Following in vitro co-culture with activated central memory cells (TCM), ~3% of the TN acquired activation/memory canonical markers (CD45RO and CD95) in an MHC-I dependent-fashion. Using scRNA-seq, we also observed that ~3% of the TN acquired an activated/memory signature, while ~84% developed a unique activated transcriptional profile hybrid between naïve and activated memory. Pseudotime trajectory analysis provided further evidence that TN with an activated/memory or hybrid phenotype were derived from TN. Our data reveal a non-cytotoxic function of TMem with potential to activate autologous TN into the activated/memory pool. These findings may have implications for host-protection and autoimmunity that arises after vaccination, infection or transplantation.

Single-cell RNA sequencing reveals distinct T cell populations in immune-related adverse events of checkpoint inhibitors

“…The contribution of this cluster to overall T cell suppression phenotype is further demonstrated through comparison of T cell suppressor signature scores between patients with arthritis and no irAEs ( Figure 5 E). Like other central memory populations, the genes in this cluster were associated with IL-3 and IL-5 secretion 24 and class I signaling 25 ( Figure 5 F).…”

Unique features of the TCR repertoire of reactivated memory T cells in the experimental mouse tumor model

“…Memory cells have a lower activation threshold than naive T cells [36] , [37] and rapidly acquire an effector state upon re-encounter with the antigen presented even at much lower doses [37] , [38] , [39] . It was also shown that memory T cells are relatively independent of co-stimulation from antigen-presenting cells (APCs) [20] , [23] .…”

Non-cytotoxic functions of CD8 T cells: “repentance of a serial killer”

“…Indeed, recently our lab showed that activated memory CD8 T cells acquire a novel non-cytotoxic function by which they can interact and influence the phenotype and transcriptome of naïve CD8 T cells. In this scenario, they acquire two states (1) an activated/memory T cell state and (2) a unique hybrid state between naïve and effector/activated memory cells ( 123 ) ( Figure 4C ). Since both cell populations were sorted from the same healthy subject, we speculate that activated memory T cells are presenting self-antigen to naïve T cells generating auto-reactive T cells.…”