Local Accumulation and Activation of Regulatory Foxp3+ CD4 TR Cells Accompanies the Appearance of Activated CD8 T Cells in the Liver

Only small populations of nonactivated, nonproliferating Foxp3(+) CD4 regulatory T cell (T-R) cells are found in the nonparenchymal cell compartment of the mouse liver while liver-draining celiac nodes contain expanded, activated TR cell populations (similar to other lymph nodes). Liver Foxp3(+) CD4 T-R cells suppress activation of T cell responses. Polyclonal, systemic T cell activation in vivo (via anti-CD3 antibody injection) is accompanied by intrahepatic accumulation of T blasts and a rapid but transient intrahepatic increase of activated, proliferating Foxp3(+) CD4 T-R cells. Following vaccination, the appearance of peripherally primed, specific CD8 T blasts in the liver is preceded by a transient rise of Foxp3(+) CD4 T-R cells in the liver. The adoptive transfer of immune CD8 T cells into congenic hosts that express the relevant antigen only in the liver leads to the accumulation of specific donor CD8 T cells and of host Foxp3(+) CD4 T-R cells in the liver. Conclusion: Although it contains only a small population of quiescent Foxp3(+) CD4 T-R cells, the liver can rapidly mobilize and/or recruit this T cell control in response to the intrahepatic appearance of peripherally or locally generated CD8 T blasts. (HEPATOLOGY 2008;48:1954-1963.)