Antigen-specific primary activation of CD8(+) T cells within the liver

It is generally accepted that naive T cells recirculate via the blood and l ymph, but do not enter nonlymphoid tissues without prior activation and dif ferentiation. In this study, we demonstrate that the liver is an exception to this rule. Naive Des-TCR transgenic CD8(+) T cells specific for H-2K(b) were selectively retained in the liver within a few minutes of adoptive tra nsfer into transgenic Met-Kh mice expressing H-2K(b) in the liver. Activate d CD8(+) cells were found in the liver, but not the blood, as soon as 2 h a fter transfer and underwent cell division and started to recirculate within 24 h of transfer. In contrast, CD8(+) cells activated in the lymph nodes r emained sequestered at that site for 2 days before entering the blood. Our results therefore suggest that, in addition to its previously described rol e as a non Ag-specific activated T cell graveyard, the liver is involved in Ag-specific activation of naive recirculating CD8(+) T cells. This particu lar property of the liver, combined with the previously demonstrated abilit y of hepatocytes to induce tolerance by means of premature CD8(+) T cell de ath, may be a major mechanism contributing to the acceptance of liver allog rafts and the chronicity of viral hepatitis.