Unconventional NK1.1- intermediate TCR cells as major T lymphocytes expanding in chronic graft-versus-host disease

Abstract

Chronic graft-versus-host disease (GVHD) accompanying autoimmune disease was induced in (C57BL/6xDBA/2) F1 mice (H-2b/d) by an injection of splenic T cells of parental DBA/2 origin (H-2d). In parallel with the onset of proteinuria, an expansion of lymphocytes was induced in the liver and kidney, showing a peak at 2 weeks after the onset of disease. The majority of lymphocytes were of recipient origin (H-2b/d). The main lymphocyte subset among T cells at the pre-onset stage and after the onset of disease was CD8+ NK1.1- CD3int cells (of extrathymic, hepatic origin) in both the liver and kidney. NK1.1- CD3int cells confer primarily neither NK-like nor NKT-like cytotoxicity. No induction of these types of cytotoxicity was observed in these mice with the expansion of NK1.1- CD3int cells. This raised the possibility that granulocytes induced in the liver and kidney might be associated with tissue damage. The present results suggest that, similarly to the case of autoimmune-prone mice with genetic background (e.g. MRL-lpr/lpr mice and BXSB mice), NK1.1- CD3int cells of extrathymic, hepatic origin might be crucial lymphocytes involved in the induction of the autoimmune-like disease in mice with chronic GVHD, in conjunction with B cells (e.g. B-1 cells).