CD8(+)CD103(+) regulatory T cells in spontaneous tolerance of liver allografts

It has been shown that rat liver allografts between certain inbred major histocompatibility complex (MHC) disparate strains are accepted spontaneously, and regulatory T cells (Tregs) have been suggested to play a role in the spontaneous liver tolerance. CD8(+)CD103(+) T cells bear the phenotypes of effector cells, and they are implicated in allograft destruction. Here we provide evidence that CD8(+)CD103(+) T cells possess regulatory function and may contribute to prevent liver allograft rejection. We show that the expression of CD103 in the CD8(+) T cells was increased in spontaneous liver grafts tolerant recipients. We further show that CD8(+)CD103(-) T cells can also upregulate the expression of CD103 and Foxp3 after stimulation with alloantigen or TGF-beta in vitro, and the CD8(+)CD103(+) T cells acquired regulatory properties. The suppressive function of the alloantigen or TGF-beta conditioned CD8(+)CD103(+) T cells was cell-cell contact dependent. These results imply that liver-specific factor(s) would be involved in the generation of CD8(+)CD103(+) Tregs that contribute to spontaneous liver allografts tolerance.