LIVER IS A POSSIBLE SITE FOR THE PROLIFERATION OF ABNORMAL CD3+4-8- DOUBLE-NEGATIVE LYMPHOCYTES IN AUTOIMMUNE MRL-LPR LPR MICE

MRL-Ipr/lpr mice develop a severe autoimmune disease that resembles systemic lupus erythematosis in humans. The predominant immunological feature in these mice is the development of peripheral lymphadenopathy due to the expansion of an unusual T cell subset (TCR α/β+5CD3+4−8−B220+), which may be related to the onset of their autoimmunity. However, it is unknown whether such abnormal lymphocytes proliferate in the specific organs or not. We demonstrated in the present study that the number of liver nonparenchymal mononuclear cells (MNC) in the diseased MRL-Ipr/Iprmice was 10 times greater than that ofcontrol MRL- +/+ mice. Moreover, the freshlyisolated liver MNC of MRL-Ipr/lpr mice vigorously proliferated in vitro and consisted of abnormal CD3+4−8− lymphocytes. Such in vitro proliferation was not observed in the MNC of other peripheral lymphoid organs. A potent natural cytotoxicity was also confined to the liver MNC in MRL-1pr/1pr mice. In vivo injection of [3H]TdR demonstrated that liver MNC incorporated [3H]TdR such incorporation showed a peak on day 1, and the MNC-incorporated [3H]TdR appeared in the lymph nodes as late as day 5 after the injection. These results suggest that the liver is a possible site for the proliferation of abnormal lymphocytes, which may migrate thereafter into the peripheral organs in MRL-Ipr/lpr mice. © 1990, Rockefeller University Press., All rights reserved.