Early-onset multifocal inflammation in the transforming growth factor β1-null mouse is lymphocyte mediated

Ronald J. Diebold, Michael J. Eis, Moying Yin, Ilona Ormsby, Greg P. Boivini, Bruce J. Darrow, Jeffrey E. Saffitz, Thomas Doetschman

Research output: Contribution to journalArticle

218 Scopus citations

Abstract

Transforming growth factor β1 (TGFβ1)-null mice die from complications due to an early-onset multifocal inflammatory disorder. We show here that cardiac cells are hyperproliferative and that intercellular adhesion molecule 1 (ICAM-1) is elevated. To determine which phenotypes are primarily caused by a deficiency in TGFβ1 from those that are secondary to inflammation, we applied immunosuppressive therapy and genetic combination with the severe combined immunodeficiency (SCID) mutation to inhibit the inflammatory response. Treatment with antibodies to the leukocyte function-associated antigen 1 doubled longevity, reduced inflammation, and delayed heart cell proliferation. TGFβ1-null SCID mice displayed no inflammation or cardiac cell proliferation, survived to adulthood, and exhibited normal major histocompatibility complex II (MHC II) and ICAM-1 levels. TGFβ1-null pups born to a TGFβ1-null SCID mother presented no gross congenital heart defects, indicating that TGFβ1 alone does not play an essential role in heart development. These results indicate that lymphocytes are essential for the inflammatory response, cardiac cell proliferation, and elevated MHC II and ICAM-1 expression, revealing a vital role for TGFβ1 in regulating lymphocyte proliferation and activation, which contribute to the maintenance of self tolerance.

Original languageEnglish (US)
Pages (from-to)12215-12219
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number26
DOIs
StatePublished - Dec 19 1995

Keywords

  • Cardiac hyperplasia
  • Severe combined immunodeficient mice

ASJC Scopus subject areas

  • General

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