Local accumulation and activation of regulatory Foxp3 + CD4 T R 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 T R 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. (H EPATOLOGY 2008;48:1954‐1963.)