Health & body · 1998
Can strongly activated immune cells travel to the liver and damage it?
Yes—in T cell receptor transgenic mice, activated T cells could migrate to the liver and damage liver cells. Activating CD8(+) T cells with a high-affinity peptide markedly increased liver lymphocytes, with extensive liver-cell damage and elevated serum aspartate transaminase; this was not observed in mice with a class II MHC-restricted T cell receptor.
Details
Little is understood about where activated T lymphocytes go in the body and what they do to the tissues they enter. Previous work had suggested that damaged lymphocytes migrate to the liver.
This study used an in vivo antigen-activation experiment comparing mice transgenic for ovalbumin-specific T cell antigen receptors (TCRs) restricted by either class I or class II major histocompatibility complex (MHC). After activation with antigen, CD4(-)CD8(-)B220(+) T cells emerged more frequently from CD8(+) precursors than from CD4(+) T cells. This change in phenotype occurred only with the high-affinity native peptide antigen, not with lower-affinity peptide variants.
Activation of CD8(+) cells with the high-affinity peptide also produced a dramatically increased number of liver lymphocytes, accompanied by extensive hepatocyte damage and elevated serum aspartate transaminase. This was not observed in mice bearing a class II MHC-restricted TCR.
The findings show that CD4(-)CD8(-)B220(+) T cells preferentially derive from CD8(+) precursors after a high-intensity TCR signal. The study concludes that, after activation, T cells can migrate to the liver and induce hepatocyte damage, thereby providing a model of autoimmune hepatitis.
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