Through positive and negative selection, the thymus allows a small fraction of immature CD4 8 double positive thymocytes to differentiate into mature CD4 8 or CD4 8 single positive cells; these cells are released into the periphery to establish the mature T cell pool. Positive selection rescues thymocytes that express TCR with low affinity for peptides bound to MHC molecules expressed on cortical epithelial cells. Conversely, negative selection eliminates thymocytes with high affinity for MHC–peptide complexes, thereby leading to self-tolerance induction (1, 2). Via this process of selection, the thymus generates a peripheral repertoire that is largely depleted of overtly autoreactive T cells but retains low but significant reactivity for self-MHC molecules. Retaining weak affinity for self-MHC/peptide ligands has generally been considered a requirement for T cells to optimally recognize foreign antigens in the context of self-MHC molecules. However, recent findings strongly suggest that low-level self-reactivity serves an additional purpose: namely, to maintain survival and homeostasis of naive T cells (for a review, see reference 3). Mature naive T cells are usually considered to remain in a dormant state unless awakened by foreign antigens expressed on activated APCs. This view has now been modified by the finding that prolonged survival of naive T cells in a resting state requires low-level TCR signaling from contact with self-MHC/peptide ligands (ie, with MHC class I molecules for CD8 cells and class II molecules for CD4 cells [4–10]). In the absence of these self-ligands, naive T cells gradually disappear. Evidence for active signaling through the TCR is also provided by the finding that survival of resting naive T cells requires expression of lung Kruppel-like factor (LKLF), a member of Kruppel-like zinc transcription factor family (11). This molecule is presumably involved in translating covert TCR signaling into cell survival cues.