Peripheral T-cell tolerance: the contribution of permissive T-cell migration into parenchymal tissues of the neonate

T lymphocytes with self-destructive capacity are often found in healthy ind ividuals, indicating efficient control mechanisms that prevent chronic auto immune deseases. Since naive T lymphocytes do not circulate through extraly mphoid tissues the concept has emerged that peripheral T cells ignore tissu e-specific antigens unless they are presented by professional antigen-prese nting cells in the lymphoid compartments. However, this view pays attention only to experiments performed in adult animals. This report reviews the ev idence that tissues of neonatal mice, in contrast to adults, exhibit high a ccessibility for naive T cells, thereby allowing the direct contact with ti ssue-specific self-antigens on parenchymal cells during neonatal life and t olerance induction to such self-antigens. In mouse bone marrow chimeras gen erated at different ages, recent thymic emigrants were tolerized to a major histocompatibility class I antigen expressed on keratinocytes only during a neonatal period and not during adulthood. Blockade of T-cell migration ne onatally prevented tolerance induction. The neonatally induced tolerance is maintained during adulthood, apparantly by a dominant regulatory mechanism . Thus, parenchymal cells and T-cell migration in the neonate contribute to the control of autoreactive T cells.