Neonatal tolerance revisited by mathematical modelling

The classical view of a neonatal tolerance window has recently been challenged by several studies showing that neonates can evoke normal immune responses. For example, neonatal immunity against the male antigen H-Y can be induced in female recipients by inoculation of male donor spleen cells enriched for professional antigen-presenting cells (APCs). In the same set- up, adult female recipients become tolerant by giving large doses of spleen cells. Using a probabilistic model, we here show how the number of T cells and endogenous APCs in the recipient, and the dose and quality of donor APCs can explain all observed phenomena. We thus reconcile the classical neonatal tolerance window with the recent data on neonatal immunity and adult tolerance.