Autoimmunity associated with TGF-β1-deficiency in mice is dependent on MHC class II antigen expression

John J. Letterio, Andrew G. Geiser, Ashok B. Kulkarni, Howard Dang, Liping Kong, Toru Nakabayashi, Crystal L. Mackall, Ronald E. Gress, Anita B. Roberts

Research output: Contribution to journalArticle

168 Scopus citations

Abstract

The progressive inflammatory process found in transforming growth factor β1 (TGF-β1)-deficient mice is associated with several manifestations of autoimmunity, including circulating antibodies to nuclear antigens, immune complex deposition, and increased expression of both class I and class II major histocompatibility complex (MHC) antigens. The contribution of MHC class II antigens to the genesis of this phenotype has been determined by crossing the TGF-β1-null [TGF-β1((-/-))] genotype into the MHC class II- deficient [MHC-II((-/-))] background. Mice homozygous for both the TGF-β1 null allele and the class II null allele [TGF-β1((-/-));MHC-II((-/-))] are without evidence of inflammatory infiltrates, circulating autoantibodies, or glomerular immune complex deposits. Instead, these animals exhibit extensive extramedullary hematopoiesis with progressive splenomegaly and adenopathy, surviving only slightly longer than TGF-β1((-/-));MHC-II((+/+)) mice. The role of CD4+ T cells, which are also absent in MHC class II-deficient mice, is directly demonstrated through the administration of anti-CD4 monoclonal antibodies in class II-positive, TGF-β1((-/-)) mice. The observed reduction in inflammation and improved survival emphasize the significance of CD4+ cells in the pathogenesis of the autoimmune process and suggest that the additional absence of class II antigens in TGF-β1((-/-));MHC-II((-/-)) mice may contribute to their extreme myeloid metaplasia. Thus, MHC class II antigens are essential for the expression of autoimmunity in TGF-β1- deficient mice, and normally may cooperate with TGF-β1 to regulate hematopoiesis.

Original languageEnglish (US)
Pages (from-to)2109-2119
Number of pages11
JournalJournal of Clinical Investigation
Volume98
Issue number9
DOIs
StatePublished - Nov 1 1996

Keywords

  • hematopoiesis
  • inflammation
  • leukocyte
  • metaplasia
  • myeloid

ASJC Scopus subject areas

  • Medicine(all)

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    Letterio, J. J., Geiser, A. G., Kulkarni, A. B., Dang, H., Kong, L., Nakabayashi, T., Mackall, C. L., Gress, R. E., & Roberts, A. B. (1996). Autoimmunity associated with TGF-β1-deficiency in mice is dependent on MHC class II antigen expression. Journal of Clinical Investigation, 98(9), 2109-2119. https://doi.org/10.1172/JCI119017