Heterogeneous Differentiation Patterns of Individual CD8 ⁺ T Cells

Abstract

Upon infection, antigen-specific CD8(+) T lymphocyte responses display a highly reproducible pattern of expansion and contraction that is thought to reflect a uniform behavior of individual cells. We tracked the progeny of individual mouse CD8(+) T cells by in vivo lineage tracing and demonstrated that, even for T cells bearing identical T cell receptors, both clonal expansion and differentiation patterns are heterogeneous. As a consequence, individual naïve T lymphocytes contributed differentially to short- and long-term protection, as revealed by participation of their progeny during primary versus recall infections. The discordance in fate of individual naïve T cells argues against asymmetric division as a singular driver of CD8(+) T cell heterogeneity and demonstrates that reproducibility of CD8(+) T cell responses is achieved through population averaging.

Antigen expression level threshold tunes the fate of CD8 T cells during primary hepatic immune responses

“…Although all OT-I T cells expressed the same TCR, they did not all express exactly the same phenotype. This result is consistent with the findings of a recent study (28) that showed that general expansion and contraction of antigen-specific CD8 T lymphocyte responses associated with robust outcomes is achieved through population averaging of discordant individual naive T-cell fates, rather than by uniform behavior of individual cells. Unbiased mathematical modeling (29) also fits the experimental data and supports the concept that complex T-cell responses are driven by stochastic processes and variability in individual cells.…”

Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development

“…However, elegant in vivo approaches using adoptive transfer systems of single murine CD8 + memory cells (Gerlach et al, 2013a;Graef et al, 2014) also argue in favor of a linear differentiation model. As similar experiments have not been conducted for CD4 + cells yet and are impossible in the human system, our data represent new insights into this topic.…”

T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?

“…Two recent papers resolved the bulk population of antigen-specific T-cells in acute infections into cells that originate from the same naïve precursor (referred to as T-cell families) 69,70 .…”