T cell recognition in chronic beryllium disease.
Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by beryllium exposure in the workplace and is characterized by the accumulation of beryllium-specific CD4(+) T cells. Depending on genetic susceptibility and the nature of the exposure, CBD occurs in up to 20% of exposed workers. Genetic susceptibility has been associated with particular HLA-DP alleles, especially those possessing a negatively charged glutamic acid residue at the 69th position of the beta-chain. The mechanism for this association lies in the ability of these HLA-DP molecules to bind and present beryllium to pathogenic CD4(+) T cells. Large numbers of effector memory, beryllium-specific CD4(+) T cells are recruited to the lung of these subjects and secrete Th1-type cytokines upon beryllium recognition. The presence of circulating beryllium-specific CD4(+) T cells directly correlates with the severity of lymphocytic alveolitis. With the presence of a known antigenic stimulus, CBD serves as an important model of immune-mediated, organ destruction. Thus, our findings in CBD have important implications for studies in autoimmune diseases, in particular those with an unknown inciting antigen and an inaccessible target organ.
Amicosante
Massimo
M
Department of Internal Medicine, University of Rome "Tor Vergata", Rome, Italy.
Fontenot
Andrew P
AP
D017951:Antigen Presentation; D001607:Berylliosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D001608:Beryllium / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006682:HLA-DP Antigens / Q000737:chemistry; D006801:Humans; D008168:Lung / Q000276:immunology; D018448:Models, Immunological; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013329:Structure-Activity Relationship
D006682:HLA-DP Antigens; D011948:Receptors, Antigen, T-Cell; D001608:Beryllium