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.
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Davenport, M.P., Smith, N.L. & Rudd, B.D. Building a T cell compartment: how immune cell development shapes function. Nat Rev Immunol 20, 499–506 (2020). https://doi.org/10.1038/s41577-020-0332-3
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