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 Glu 69 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.

HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease / G., Lombardi; C., Germain; J., Uren; Fiorillo, Maria Teresa; R. M., Du Bois; W., Jones Williams; C., Saltini; Sorrentino, Rosa; R., Lechler. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 166:5(2001), pp. 3549-3555.

HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease

FIORILLO, Maria Teresa;SORRENTINO, Rosa;
2001

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 Glu 69 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.
2001
01 Pubblicazione su rivista::01a Articolo in rivista
HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease / G., Lombardi; C., Germain; J., Uren; Fiorillo, Maria Teresa; R. M., Du Bois; W., Jones Williams; C., Saltini; Sorrentino, Rosa; R., Lechler. - In: JOURNAL OF IMMUNOLOGY. - ISSN 0022-1767. - 166:5(2001), pp. 3549-3555.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/129074
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