Expansion of the population of double negative CD4-8- T alpha beta-cells in the liver is a common feature of autoimmune mice.
There have been several reports that double negative (DN) CD4-8- T alpha beta-cells might be responsible for the onset of autoimmune diseases in humans and mice. We previously revealed that such DN T alpha beta-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+ alpha beta-cells. Identification of DN T alpha beta-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 T alpha beta-cells (greater than 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 T alpha beta-cells (less than 10%) in the liver. Among autoimmune mice, MRL-lpr/lpr and C3H/HeJ-gld/gld mice had lymphadenopathy, which consisted of DN T alpha beta-cells (greater than 25%), after the onset of disease. Autoimmune mice of the other strains had neither lymphadenopathy nor DN T alpha beta-cells in the periphery, even when they were diseased. These results suggest that the expansion of the DN T alpha beta-cell population in the liver is a common feature of autoimmune mice, irrespective of the information of lymphadenopathy.
Masuda
T
T
Second Department of Pathology, Tohoku University School of Medicine, Japan.
Ohteki
T
T
Abo
T
T
Seki
S
S
Nose
S
S
Nagura
H
H
Kumagai
K
K
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016201:Receptors, Lymphocyte Homing / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016201:Receptors, Lymphocyte Homing