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-K(b)-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 K(b)-specific graft rejection by naive CD8(+) T cells. Third-party immune responses remain unaffected. Up-regulation of TGF-beta 1 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.