Interstitial pneumonitis and hepatitis after transfer of bone marrow cells bearing the lpr gene to irradiated recipients: a disease due to large granular leucocytes?

Abstract

Mice bearing the 'auto-immune' lpr gene develop a lympho-proliferative disease associated with the production of various antibodies. Lethally irradiated recipients were grafted with bone marrow cells (BMC) from syngeneic mice with or without the lpr gene. After 6 months, the survivors were 0/24 and 16/20 for the recipients of lpr and normal BMC respectively. The mortality rate was independent of the presence of T lymphocytes among the BMC. Histological evaluation showed that hepatitis, interstitial pneumonitis, and sclerosis of lymphohaemopoietic organs were the major causes of death for the recipients of lpr BMC. Hepatitis was associated with an increase in the number of liver interstitial cells (LIC) from about 2 X 10(6) up to about 10(7) cells per liver. The LIC associated with the hepatitis were composed of polymorphonuclear leucocytes and large mononuclear leucocytes, showing phenotypic (i.e. Thy.1+, asialo GM1, presence of cytoplasmic granules) and functional (i.e. non-phagocytic and cytolytic) properties of NK cells. The disease can be distinguished both from the spontaneous disease of the lpr mice (by the absence of 'lpr cells' and of anti-DNA antibodies) and from graft versus host disease by the absence of cutaneous and intestinal lesions. It may represent a model of tissue injury mediated by large granular leucocytes.