The smallest unit: Effector and memory CD8⁺ T cell differentiation on the single cell level

CD8⁺ T cell immune responses provide immediate protection against primary infection and durable memory capable of rapidly fighting off re-infection. Immediate protection and lasting memory are implemented by phenotypically and functionally distinct T cell subsets. While it is now widely accepted that these diverge from a common source of naïve T cells (T_n), the developmental relation and succession of effector and memory T cell subsets is still under intense debate. Recently, a distinct memory T cell subset has been suggested to possess stem cell-like features, sparking the hope to harness its capacity for self-renewal and diversification for successful therapy of chronic infections or malignant diseases. In this review we highlight current developmental models of memory generation, T cell subset diversification and T cell stemness. We discuss the importance of single cell monitoring techniques for adequately mapping these developmental processes and take a brief look at signaling components active in the putative stem cell-like memory T cell compartment.