Expansion of intermediate T-cell receptor cells in mice with autoimmune-like graft-versus-host disease

Chronic graft-versus-host disease (GVHD) following bone marrow transplantation often gives rise to a severe autoimmune-like state. To investigate the immunopathogenesis of this diseased state, mice receiving a transplant of lymphocytes with major histocompatibility complex (MHC) class II disparity (the simplest model of chronic GVHD) were examined. (B10.Thy-1.1 x B6.C-H-2bm12) F1 mice were injected with parental B10.Thy-1.1 CD4+ splenic T cells. These mice showed intensive lymphocyte infiltration of the target organs, including the liver, salivary glands and pancreas. Indeed, the cell numbers yielded from the spleen and liver were increased, and polyclonal B-cell activation was induced by 14 days after injection. More strikingly, more than 80% of such expanding lymphocytes in the target organs became T cells with T-cell receptors (TCR) of intermediate intensity (i.e. intermediate TCR cells) that carried the properties of extrathymic origin. Despite the homogeneous expansion of intermediate TCR cells in GVHD mice, these T cells were polyclonal in terms of V beta usage. These results, in conjunction with the data using the thymectomized mice as recipients, suggested that extrathymic, intermediate TCR cells possibly of recipient origin might be intimately related to the pathogenesis of the autoimmune-like state resulting from chronic GVHD.