Control of peripheral T-lymphocyte tolerance in neonates and adults

Neonatal life is a unique developmental stage, in which the peripheral T-lymphocyte pool is evolving in a lymphopenic environment and the freshly generated T lymphocytes are extensively migrating through non-lymphoid tissues. Here, we emphasize the consequences of neonatal lymphopenia and tissue accessibility for T-lymphocyte tolerance induction. We propose that self-destructive T-lymphocyte responses are prevented in the neonate by limiting homeostatic T-lymphocyte expansion and thereby the activation of potentially autodestructive memory T lymphocytes. Furthermore, the extensive migration through tissues might lead to a dominant form of tolerance in the neonatal phase, which is maintained throughout adult life, during which the tissues are no longer readily accessible to T lymphocytes. Thus, it is not only dendritic cells that are crucial for self-tolerance: neonatal mechanisms are also required.