Open AccessRegulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic murine model of beryllium-induced disease
Author(s) -
Douglas G. Mack,
Michael T. Falta,
Amy S. McKee,
Arlan D. Martin,
Philip L. Simonian,
Frances Crawford,
Terry Gordon,
Robert R. Mercer,
Mark D. Hoover,
Philippa Marrack,
John W. Kappler,
Rubin M. Tuder,
Andrew P. Fontenot
Publication year - 2014
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1408048111
Subject(s) - major histocompatibility complex , transgene , genetically modified mouse , immunology , immune system , biology , inflammation , disease , human leukocyte antigen , allele , gene , genetics , microbiology and biotechnology , antigen , medicine , pathology
Significance Genetic linkage to major histocompatibility complex class II proteins has been observed in many immunological disorders; yet, little is known about the underlying mechanisms of these associations. For chronic beryllium disease (CBD), the linkage toHLA-DPB1 alleles encoding a glutamic acid at position 69 of the β-chain is well established. We tested whether the presence of HLA-DP2 is sufficient for the development of a disease-specific model of CBD. HLA-DP2 transgenic mice developed a beryllium-specific adaptive immune response composed of CD4+ T cells that secrete Th1-type cytokines and are HLA-DP2-restricted, thus replicating the major features of the human disease. In addition, regulatory T cells modulate granuloma formation in the lungs of beryllium oxide-exposed HLA-DP2 transgenic mice.
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