HLA-DP Allele-Specific T Cell Responses to Beryllium Account for DP-Associated Susceptibility to Chronic Beryllium Disease

Journal of Immunology - Tập 166 Số 5 - Trang 3549-3555 - 2001
Giovanna Lombardi1,2, Conrad Germain1, Julia Uren1, Maria Teresa Fiorillo3, Ronald M. du Bois4, W. Jones-Williams5, Cesare Saltini6, Rosa Sorrentino3, Robert I. Lechler1
1*Department of Immunology, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom;
2Immunoregulation & Immune Intervention
3†Department of Cell Biology and Development, University “La Sapienza”, Rome, Italy;
4Royal Brompton Hospital, London, United Kingdom
5§Department of Medicine, University of Wales College of Medicine, Cardiff, United Kingdom; and
6¶Division of Respiratory Diseases of the University of “Tor Vergata” at the L. Spallanzani Hospital, Institute for Research and Clinical Care, Rome, Italy

Tóm tắt

Abstract Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions. Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in ∼3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DPβ-chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DPβ69. Furthermore, the proliferative responses of the clones were absolutely dependent upon DPβ Glu69 in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-γ (Th1) and little or no IL-4 (Th2) cytokines. This study provides insights into the molecular basis of DP2-associated susceptibility to CBD.

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Tài liệu tham khảo

Nemery, B.. 1990. Metal toxicity and the respiratory tract. Eur. Respir. J. 3: 202

Freiman, D. G., H. L. Hardy. 1970. Beryllium disease: the relation of pulmonary pathology to clinical course and prognosis based on a study of 130 cases from the U.S. beryllium case registry. Hum. Pathol. 1: 25

Hardly, H. L., J. R. Tabershaw. 1946. Delayed chemical pneumonitis occurring in workers exposed to beryllium compounds. J. Ind. Hyg. Toxicol. 28: 197

Eisenbud, M., J. Lisson. 1983. Epidemiological aspects of beryllium-induced nonmalignant lung disease: a 30-year update. J. Occup. Med. 25: 196

Kreiss, K., F. Miller, L. S. Newman, E. A. Ojo-Amaize, M. D. Rossman, C. Saltini. 1994. Chronic beryllium disease—from the workplace to cellular immunology, molecular immunogenetics, and back. Clin. Immunol. Immunopathol. 71: 123

Fischbein, A., J. C. Luo, S. J. Solomon, S. Horowitz, W. Hailoo, A. Miller. 1992. Clinical findings among hard metal workers. Br. J. Ind. Med. 49: 17

Hanifin, J. M., W. L. Epstein, M. J. Cline. 1970. In vitro studies on granulomatous hypersensitivity to beryllium. J. Invest. Dermatol. 55: 284

Saltini, C., K. Winestock, M. Kirby, P. Pinkston, R. G. Crystal. 1989. Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells. N. Engl. J. Med. 320: 1103

Saltini, C., M. Kirby, B. C. Trapnell, N. Tamura, R. G. Crystal. 1990. Biased accumulation of T lymphocytes with “memory”-type CD45 leukocyte common antigen gene expression on the epithelial surface of the human lung. J. Exp. Med. 171: 1123

Romagnoli, P., G. A. Spinas, F. Sinigaglia. 1992. Gold-specific T cells in rheumatoid arthritis patients treated with gold. J. Clin. Invest 89: 254

Sinigaglia, F., D. Scheidegger, G. Garotta, R. Scheper, M. Pletscher, A. Lanzavecchia. 1985. Isolation and characterization of Ni-specific T cell clones from patients with Ni-contact dermatitis. J. Immunol. 135: 3929

Theofilopoulos, A. N.. 1995. The basis of autoimmunity. II. Genetic predisposition. Immunol. Today 16: 150

Richeldi, L., R. Sorrentino, C. Saltini. 1993. HLA-DPB1 glutamate 69: a genetic marker of beryllium disease. Science 262: 242

Richeldi, L., K. Kreiss, M. M. Mroz, B. Zhen, P. Tartoni, C. Saltini. 1997. Interaction of genetic and exposure factors in the prevalence of berylliosis. Am. J. Ind. Med. 32: 337

Potolicchio, I., G. Mosconi, A. Forni, B. Nemery, P. Seghizzi, R. Sorrentino. 1997. Susceptibility to hard metal lung disease is strongly associated with the presence of glutamate 69 in HLA-DP β chain. Eur. J. Immunol. 27: 2741

Chomczynski, P., N. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162: 156

Ferradini, L., S. Roman-Roman, J. Azocar, H. Michalaki, F. Triebel, T. Hercend. 1991. Studies on the human T cell receptor α/β variable region genes. II. Identification of four additional V β subfamilies. Eur. J. Immunol. 21: 935

Drenou, B., V. Blancheteau, D. H. Burgess, R. Fauchet, D. J. Charron, N. A. Mooney. 1999. A caspase-independent pathway of MHC class II antigen-mediated apoptosis of human B lymphocytes. J. Immunol. 163: 4115

Tinkle, S. S., L. A. Kittle, B. A. Schumacher, L. S. Newman. 1997. Beryllium induces IL-2 and IFN-γ in berylliosis. J. Immunol. 158: 518

Fontenot, A. P., M. T. Falta, B. M. Freed, L. S. Newman, B. L. Kotzin. 1999. Identification of pathogenic T cells in patients with beryllium-induced lung disease. J. Immunol. 163: 1019

Sollid, L. M., G. Markussen, J. Ek, H. Gjerde, F. Vartdal, E. Thorsby. 1989. Evidence for a primary association of celiac disease to a particular HLA-DQ α/β heterodimer. J. Exp. Med. 169: 345

Lundin, K. E., H. Scott, T. Hansen, G. Paulsen, T. S. Halstensen, O. Fausa, E. Thorsby, L. M. Sollid. 1993. Gliadin-specific, HLA-DQ (α 1*0501, β 1*0201) restricted T cells isolated from the small intestinal mucosa of celiac disease patients. J. Exp. Med. 178: 187

Bugawan, T. L., G. Angelini, J. Larrick, S. Auricchio, G. B. Ferrara, H. A. Erlich. 1989. A combination of a particular HLA-DP β allele and an HLA-DQ heterodimer confers susceptibility to celiac disease. Nature 339: 470

Easteal, S., M. R. Kohonen-Corish, P. Zimmet, S. W. Serjeantson. 1990. HLA-DP variation as additional risk factor in IDDM. Diabetes 39: 855

Begovich, A. B., T. L. Bugawan, B. S. Nepom, W. Klitz, G. T. Nepom, H. A. Erlich. 1989. A specific HLA-DP β allele is associated with pauciarticular juvenile rheumatoid arthritis but not adult rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 86: 9489

Carthy, D., A. MacGregor, A. Awomoi, A. S. Rigby, W. Thomson, R. Donn, A. Silman, W. Ollier. 1995. HLA-DPB1*0201 is associated with particular clinical features of rheumatoid arthritis. Rev. Rhum. Engl. Ed. 62: 163

Stephens, H. A., R. W. Vaughan, L. I. Sakkas, K. I. Welsh, G. S. Panayi. 1989. Southern blot analysis of HLA-DP gene polymorphisms in Caucasoid rheumatoid arthritis (RA) patients and controls. Immunogenetics 30: 149

Ploski, R., B. Flato, O. Vinje, W. Maksymowych, O. Forre, E. Thorsby. 1995. Association to HLA-DRB1*08, HLA-DPB1*0301 and homozygosity for an HLA-linked proteasome gene in juvenile ankylosing spondylitis. Hum. Immunol. 44: 88

Mella, J. G., E. Roschmann, K. P. Maier, B. A. Volk. 1995. Association of primary biliary cirrhosis with the allele HLA-DPB1*0301 in a German population. Hepatology 21: 398

Taylor, G. M., M. D. Robinson, A. Binchy, J. M. Birch, R. F. Stevens, P. M. Jones, T. Carr, S. Dearden, D. A. Gokhale. 1995. Preliminary evidence of an association between HLA-DPB1*0201 and childhood common acute lymphoblastic leukaemia supports an infectious aetiology. Leukemia 9: 440

Stephens, H. A., A. E. Brown, D. Chandanayingyong, H. K. Webster, M. Sirikong, P. Longta, R. Vangseratthana, D. M. Gordon, S. Lekmak, E. Rungruang. 1995. The presence of the HLA class II allele DPB1*0501 in ethnic Thais correlates with an enhanced vaccine-induced antibody response to a malaria sporozoite antigen. Eur. J. Immunol. 25: 3142

Magzoub, M. M., H. A. Stephens, J. A. Sachs, P. A. Biro, S. Cutbush, Z. Wu, G. F. Bottazzo. 1992. HLA-DP polymorphism in Sudanese controls and patients with insulin-dependent diabetes mellitus. Tissue Antigens 40: 64

Yamagata, K., T. Hanafusa, H. Nakajima, M. Sada, H. Amemiya, K. Tomita, J. Miyagawa, T. Noguchi, T. Tanaka, N. Kono. 1991. HLA-DP and susceptibility to insulin-dependent diabetes mellitus in Japanese. Tissue Antigens 38: 107

Stastny, P., X. J. Gao, M. Fernandez-Vina. 1991. Immunogenetics of rheumatoid arthritis and juvenile arthritis. Recenti Prog. Med. 82: 409

Todd, J. A., H. Acha-Orbea, J. I. Bell, N. Chao, Z. Fronek, C. O. Jacob, M. McDermott, A. A. Sinha, L. Timmerman, L. Steinman. 1988. A molecular basis for MHC class II-associated autoimmunity: [Published erratum appears in 1988 Science 241:888.]. Science 240: 1003

Colonna, M., W. Mantovani, G. R. Corazza, P. Barboni, G. Gasbarrini, G. B. Ferrara, R. Tosi, N. Tanigaki. 1990. Reassessment of HLA association with celiac disease in special reference to the DP association. Hum. Immunol. 29: 263

Fugger, L., L. P. Ryder, N. Morling, N. Odum, J. Friis, F. K. Pedersen, C. Heilmann, M. Sandberg-Wollheim, A. Svejgaard. 1990. DNA typing for HLA-DPB1*02 and -DPB1*04 in multiple sclerosis and juvenile rheumatoid arthritis. Immunogenetics 32: 150

Todd, J. A., J. I. Bell, H. O. McDevitt. 1987. HLA-DQ β gene contributes to susceptibility and resistance to insulin-dependent diabetes mellitus. Nature 329: 599

Greenlaw, R., P. Robinson, T. Heaton, G. Lombardi, R. Lechler. 1992. Transfection of HLA-DR-expressing DAP.3 cells with a cDNA clone encoding the glycosyl phosphatidylinositol-linked form of lymphocyte function associated antigen-3: biochemical features and functional consequences. Int. Immunol. 4: 673

Lombardi, G., S. Sidhu, J. R. Lamb, J. R. Batchelor, R. I. Lechler. 1989. Co-recognition of endogenous antigens with HLA-DR1 by alloreactive human T cell clones. J. Immunol. 142: 753

Wang, Z., P. S. White, M. Petrovic, O. L. Tatum, L. S. Newman, L. A. Maier, B. L. Marrone. 1999. Differential susceptibilities to chronic beryllium disease contributed by different Glu69 HLA-DPB1 and -DPA1 alleles. J. Immunol. 163: 1647

Brown, J. H., T. S. Jardetzky, J. C. Gorga, L. J. Stern, R. G. Urban, J. L. Strominger, D. C. Wiley. 1993. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364: 33

Stern, L. J., J. H. Brown, T. S. Jardetzky, J. C. Gorga, R. G. Urban, J. L. Strominger, D. C. Wiley. 1994. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 368: 215

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Journal of Immunology

Tập 166 Số 5

3549-3555

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