The origin of diversity: Studying the evolution of multi-faceted CD8 ⁺ T cell responses

During the past two decades of research in T cell biology, an increasing number of distinct T cell subsets arising during the transition from naý̈ve to antigen-experienced T cells have been identified. Recently, it has been appreciated that, in different experimental settings, distinct T cell subsets can be generated in parallel within the same immune response. While signals driving a single ''lineage'' path of T cell differentiation are becoming increasingly clear, it remains largely enigmatic how the phenotypic and functional diversification creating a multi-faceted T cell response is achieved. Here, we review current literature indicating that diversification is a stable trait of CD8 ⁺ T cell responses. We showcase novel technologies providing deeper insights into the process of diversification among the descendants of individual T cells, and introduce two models that emphasize either intrinsic noise or extrinsic signals as driving forces behind the diversification of single cellderived T cell progeny populations in vivo.