T cells learn quickly

Abstract

Young T cells are fast learners, according to McCaughtry et al. (page 2513). They finish part of their schooling in the thymus in just four days. Upon entering the thymus, young T cells are first tested for correctly rearranged T cell receptors (TCRs). Those that pass the exam are selected for further training in the thymic medulla. There, T cells that react to self-antigens are killed off. The rest graduate into functional, proliferating adults. This training program was previously estimated to last for two to three weeks. This notion was based on methods that did not differentiate between young T cells, mature T cells that reentered the thymus, and other thymic TCR-bearing immune cell subsets. McCaughtry and colleagues now reanalyze the kinetics of T cell training with this distinction in mind. Maturation stages were identified by specific markers and by labeling proliferating cells with BrdU. The results revealed that T cells took just four days to pass through the medulla and enter the circulation. The team also found that T cells were educated on a first-come, first-served basis. As they passed the first selection test, the cells shut off expression of a fluorescent protein, resulting in a gradual decrease in brightness. Only dim cells expressed receptors that mark exiting cells, suggesting that the emigration follows a first-in, first-out assembly-line pattern. The authors now want to understand how the plumbing of the thymus helps T cells so rapidly sample the different self-antigens expressed by each epithelial cell.