Building a T cell compartment: how immune cell development shapes function

The authors describe how the naive T cell compartment is built across a lifetime. They propose that functional diversity among naive T cells is linked to when they were created. Naive T cells adapt to meet changes in the external environment at different stages of life, persist into adulthood and contribute to the T cell compartment in adults. We are just beginning to understand the diversity of the peripheral T cell compartment, which arises from the specialization of different T cell subsets and the plasticity of individual naive T cells to adopt different fates. Although the progeny of a single T cell can differentiate into many phenotypes following infection, individual T cells are biased towards particular phenotypes. These biases are typically ascribed to random factors that occur during and after antigenic stimulation. However, the T cell compartment does not remain static with age, and shifting immune challenges during ontogeny give rise to T cells with distinct functional properties. Here, we argue that the developmental history of naive T cells creates a 'hidden layer' of diversity that persists into adulthood. Insight into this diversity can provide a new perspective on immunity and immunotherapy across the lifespan.