Liver damage preferentially results from CD8(+) T cells triggered by high affinity peptide antigens.
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 histocompatibility complex (MHC)-restricted ovalbumin-specific T cell antigen receptor (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. Furthermore, this change in phenotype is conferred only by the high affinity native peptide antigen and not by lower affinity peptide variants. After activation of CD8(+) cells with only the high affinity peptide, there is also a dramatically increased number of liver lymphocytes with accompanying extensive hepatocyte damage and elevation of 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 a CD8(+) precursor after a high intensity TCR signal. After activation, T cells can migrate to the liver and induce hepatocyte damage, and thereby serve as a model of autoimmune hepatitis.
Russell
J Q
JQ
Immunobiology Program, Department of Medicine, The University of Vermont College of Medicine, Burlington 05405, USA.
Morrissette
G J
GJ
Weidner
M
M
Vyas
C
C
Aleman-Hoey
D
D
Budd
R C
RC
D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000494:pharmacology*; D015704:CD4 Antigens / Q000096:biosynthesis; D016827:CD8 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D048429:Cell Size / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007274:Injections, Intraperitoneal; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology*
D000941:Antigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D010455:Peptides; D010047:Ovalbumin; D017493:Leukocyte Common Antigens