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Our understanding of how T cells further differentiate into various subsets with characteristic functional properties has recently expanded significantly. Nevertheless, there is still much to be learned regarding the regulatory mechanisms controlling the destiny of naïve T cells which have not yet interacted with antigens in the periphery.

The T‐cell repertoire is first shaped by thymic selection (positive and negative; see Chapter 10). Naïve, fully mature CD4⁺ and CD8⁺ T cells emerging from the thymus are poised to interact, and be activated by antigens for which their TCRs are specific. They typically live for 1–3 months and their survival requires signals from antigen receptors and cytokines, particularly IL‐7. Naïve T cells recirculate from blood through a lymph node and back to blood every 12–24 hours. It is estimated that about 1 in 100,000 naïve T cells is likely to respond to any given antigen. Hence, this rapid recirculation increases the chances that a T cell will encounter the antigen recognized by its TCR. Table 2.1 summarizes the major properties of naïve CD4⁺and CD8⁺ cells.