Proliferation and apoptosis of B220+CD4-CD8-TCR alpha beta intermediate T cells in the liver of normal adult mice: implication for lpr pathogenesis.

Small numbers of T cells have been isolated from the normal mouse liver and many of these are of the CD4-CD8-TCR alpha beta+ phenotype. Larger numbers of such cells are present in the livers of mice homozygous for the lpr mutation and the liver has been proposed to be the site of an extrathymic T cell development pathway that is expanded in lpr/lpr mice. Using a modified separation procedure that increases the liver T cell yield, we have been able to characterize a subset of CD4-CD8-TCR alpha beta intermediate T cells that express the B220 epitope of the CD45 molecule, and resemble in this and many other ways the accumulating T cells in lpr lymph nodes. These cells are an actively dividing population and even in healthy, unmanipulated mice a large proportion of them are undergoing apoptosis. We propose the model that the normal liver is a major site for T cell destruction and that the lpr defect results in failure of this process with leakage of B220+CD4-CD8-TCR alpha beta+ cells from the liver to peripheral lymphoid tissues, particularly lymph nodes.