Up-regulation of cytokine mRNA, adhesion molecule proteins, and MHC class II proteins in salivary glands of TGF-β1 knockout mice: MHC class II Is a factor in the pathogenesis of TGF-β1 knockout mice

Toru Nakabayashi, John J. Letterio, Andrew G. Geiser, Liping Kong, Noriyoshi Ogawa, Weiguo Zhao, Takao Koike, Gabriel Fernandes, Howard Dang, Norman Talal

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37 Scopus citations

Abstract

Mice homozygous for a disrupted TGF-β1 allele develop multiple lymphoproliferative disorders similar to those seen in the pseudolymphoma of Sjögren's syndrome. At 2 wk of age, these TGF-β1 mutant mice begin to develop wasting syndrome and die at around 4 to 5 wk of age. We studied salivary glands from symptomatic mutant mice > 14 days of age. Reverse transcriptase-PCR analysis showed up-regulation of proinflammatory cytokine genes such as IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, and IFN-γ in these mutant mice. Enhanced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1), and MHC class II as well as CD4-positive T lymphocyte infiltration was detected by immunostaining. To elucidate the role of MHC class II, salivary glands from TGF-β1/MHC class II double knockout mice were used to investigate the expression of adhesion molecules and MHC class II. In spite of the existence of basal intercellular adhesion molecule-1 expression on vessels, there was neither MHC class II expression, enhanced vascular cell adhesion molecule-1 expression, nor lymphocytic infiltration in the salivary glands. These results suggest that MHC class II plays a significant role in the pathogenesis of TGF-βl mutant mice. Although the mechanism that initiates multiple inflammatory diseases in these mice remains unclear, the context reported here would provide insight into the immunopathology of Sjögren's syndrome.

Original languageEnglish (US)
Pages (from-to)5527-5535
Number of pages9
JournalJournal of Immunology
Volume158
Issue number11
StatePublished - 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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