Fig. 1: Quiescence begins to be established in the DP thymocyte stage and completed in fully matured naive T cells.

During circulation, multiple factors contribute to the maintenance of quiescence in naive T cells. Trafficking molecules (S1P1, CD62L and CCR7) guide T cell circulation, leading T cells to encounter diverse factors involved in the maintenance of quiescence. S1P, abundant in blood, directs egress of T cells from lymphoid organs and promote the survival of quiescent T cells via its receptor S1P1. Tonic TCR stimulation occurs in lymphoid organs by the engagement of self-peptide bearing MHC molecules and facilitate T cell quiescence. High level of IL-7 in periphery also supports the survival of T cells and prevent quiescence exit through IL-7R. Intrinsic regulators programmed in quiescent T cells coordinate these extrinsic signals for optimal maintenance of quiescence. DP, CD4⁺CD8⁺ double positive; SP, CD4⁺ or CD8⁺ single positive.