CTL access to tissue antigen is restricted in vivo

Kazuki Ando, Luca G. Guidotti, Andreas Cerny, Tetsuya Ishikawa, Francis V. Chisari

Research output: Contribution to journalArticle

Abstract

MHC class I-restricted, hepatitis B surface Ag (HBsAg)-specific, CD8+ polyclonal CTL lines and clones caused severe necroinflammatory liver disease when they are injected i.v. into transgenic mice that display widespread tissue expression of HBsAg. Surprisingly, the same CTLs fail to cause disease in any other HBsAg-positive tissue in these animals. However, the CTLs are highly cytopathic for HBsAg-positive renal tubules and choroid plexus epithelial cells when they are injected extravascularly, either beneath the kidney capsule or intracerebrally. Analysis of the microvascular anatomy of these tissues reveals that the hepatic sinusoid is characterized by a discontinuous endothelium and the absence of a basement membrane. In contrast, the vasculature of most other tissues displays a continuous endothelium and basement membrane; and the epithelial cells of many of these tissues are also surrounded by a separate basement membrane. These results suggest that viral, tumor, and normal self Ags expressed in the liver are readily accessible to class I-restricted T cells, whereas the vascular endothelium and/or the vascular and cellular basement membranes constitute an extremely effective barrier that precludes CTL access to tissue Ag at many other sites. Because class I-restricted Ag recognition occurs throughout the body in many natural diseases and disease models, the vascular barrier must be breached by other events before CTL access to endogenously synthesized epithelial Ag can occur.

Original languageEnglish
Pages (from-to)482-488
Number of pages7
JournalJournal of Immunology
Volume153
Issue number2
Publication statusPublished - Jul 15 1994

ASJC Scopus subject areas

  • Immunology

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    Ando, K., Guidotti, L. G., Cerny, A., Ishikawa, T., & Chisari, F. V. (1994). CTL access to tissue antigen is restricted in vivo. Journal of Immunology, 153(2), 482-488.