CD8 ⁺ regulatory T cells generated by neonatal recognition of peripheral self-antigen

In comparison with CD4+ regulatory T cells, the generation and function of immunomodulatory CD8+T cells is less well defined. Here we describe the existence of regulatory anti-Kb-specific CD8+ T cells that are rendered tolerant during neonatal life via antigen contact exclusively on keratinocytes. These regulatory T cells maintain tolerance during adulthood as they prevent Kb-specific graft rejection by naïve CD8+ T cells. Third-party immune responses remain unaffected. Up-regulation of TGF-beta1 and granzyme B in the regulatory CD8+ T cell population suggests the involvement of these molecules in common suppressive pathways shared with CD4+ regulatory T cells. In summary, CD8+ regulatory T cells can be induced extrathymically through antigen contact on neonatally accessible parenchymal cells and maintain tolerance throughout adult life.