The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1998/9/1147/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 6, September 21, 1998 1147-1157

Articles

Liver Damage Preferentially Results from CD8+ T Cells Triggered by High Affinity Peptide Antigens

Jennifer Q. Russell, Gregory J. Morrissette, Mark Weidner, Chirag Vyas, Deborah Aleman-Hoey, and Ralph C. Budd

From the Immunobiology Program, Department of Medicine, The University of Vermont College of Medicine, Burlington, Vermont 05405

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.

Key Words: liver lymphocytes • autoimmune hepatitis • T cell development • apoptosis • T cell antigen receptor transgenic mice

Address correspondence to Ralph C. Budd, The University of Vermont College of Medicine, Given Medical Bldg., Burlington, VT 05405-0068. Phone: 802-656-2286; Fax: 802-656-3854; E-mail: rbudd{at}zoo.uvm.edu

Abbreviations used: AST, aspartate transaminase; BCS, bovine calf serum; OVAI, OVA peptide SIINFEKL restricted to H-2Kb; OVAII, OVA peptide ISQAVHAAHAEINEAGR restricted to I-Ad.


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