T cell plasticity during lineage commitment. Lymphoid precursors exit the bone marrow and migrate to the thymus, where they differentiate into mature T cells. Rag1/2-dependent TCR rearrangement gives rise to TCRγδ and TCRαβ lineages, while MHC restriction and TCR strength leads to CD4 or CD8 commitment of the TCRαβ lineage in a Runx3- and ThPOK-dependent manner. Mature CD4 and CD8 T cells exit the thymus and receive further activation and differentiation signals in secondary lymphoid organs and nonlymphoid tissues. Each commitment step is generally associated with loss of cell plasticity, although migration to particular tissue or effector sites may allow reacquisition of various levels of plasticity, depending on the target tissue, contexts, and intratissue microenvironments.