LIVER-DAMAGE PREFERENTIALLY RESULTS FROM CD8(-CELLS TRIGGERED BY HIGH-AFFINITY PEPTIDE ANTIGENS() T)

Little is understood of the anatomical fate of activated T lymphocytes and the consequences they have on the tissues into which they migrate . Previous work has suggested that damaged lymphocytes migrate to the liver. This study compares class I versus class II major histocompatib ility complex (MHC)-restricted ovalbumin-specific T cell antigen recep tor (TCR) transgenic mice to demonstrate that after in vivo activation with antigen the emergence of CD4(-)CD8(-)B220(+) T cells occurs more frequently from a CD8(+) precursor than from CD4(+) T cells. Furtherm ore, this change in phenotype is conferred only by the high affinity n ative peptide antigen and not by lower affinity peptide variants. Afte r activation of CD8(+) cells with only the high affinity peptide, ther e is also a dramatically increased number of liver lymphocytes with ac companying extensive hepatocyte damage and elevation of serum aspartat e transaminase. This was not observed in mice bearing a class II MHC-r estricted TCR. The findings show that CD4-CD8-B220+ T cells preferenti ally derive from a CD8+ precursor after a high intensity TCR signal. A fter activation, T cells can migrate to the liver and induce hepatocyt e damage, and thereby serve as a model of autoimmune hepatitis.