Expansion of the population of double negative CD4^-8^- Tαβ-cells in the liver is a common feature of autoimmune mice

There have been several reports that double negative (DN) CD4^-8^- Tαβ-cells might be responsible for the onset of autoimmune diseases in humans and mice. We previously revealed that such DN Tαβ-cells are generated in the liver of autoimmune MRL-lpr/lpr mice. In the present study, we further characterize the histology of the liver in these mice by light and electron microscopic studies. An intensive accumulation of mononuclear cells in the liver was demonstrated and a significant proportion of these mononuclear lymphocytes was found to intimately interact with Kupffer cells or endothelial cells of the hepatic sinusoids. The majority of such lymphocytes were TcR⁺CD4^-8^-Pgp-1⁺αβ-cells. Identification of DN Tαβ-cells was then performed in various autoimmune model mice. Interestingly, all autoimmune mice tested (i.e., MRL-lpr/lpr, C3H/HeJ-gld/gld, BXSB, NOD, MRL-+/+ and NZB/W F₁ mice), showed an increased proportion of DN Tαβ-cells (>11% among all MNC) in the liver when they became old and diseased. On the other hand, young and old normal mice and young autoimmune mice before the onset of disease did not have such a high proportion of DN Tαβ-cells (<10%) in the liver. Among autoimmune mice, MRL-lpr/lpr and C3H/HeJ-gld/gld mice had lymphadenopathy, which consisted of DN Tαβ-cells (>25%), after the onset of disease. Autoimmune mice of the other strains had neither lymphadenopathy nor DN Tαβ-cells in the periphery, even when they were diseased. These results suggest that the expansion of the DN Tαβ-cell population in the liver is a common feature of autoimmune mice, irrespective of the formation of lymphadenopathy.