Local accumulation and activation of regulatory Foxp3+ CD4 TR cells accompanies the appearance of activated CD8 T cells in the liver

Abstract

Only small populations of nonactivated, nonproliferating Foxp3+ CD4 regulatory T cell (TR) 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 TR 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 TR cells. Following vaccination, the appearance of peripherally primed, specific CD8 T blasts in the liver is preceded by a transient rise of Foxp3+ CD4 TR 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 TR cells in the liver. Conclusion: Although it contains only a small population of quiescent Foxp3+ CD4 TR 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. Copyright © 2008 by the American Association for the Study of Liver Diseases.