{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:08:19Z","timestamp":1770336499850,"version":"3.49.0"},"reference-count":27,"publisher":"European Respiratory Society (ERS)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2002,6,12]]},"published-print":{"date-parts":[[2002,11]]},"abstract":"<jats:p>Berylliosis is a granulomatous disorder of the lung caused by inhalation of beryllium (Be) and dominated by the accumulation of CD4+ T-helper (Th)1 memory T-cells proliferating in response to Be in the lower respiratory tract. Two gene markers have been associated with susceptibility to berylliosis: 1) the human leucocyte antigen (HLA)-DP gene whose allelic variants, carrying glutamate in position 69 of the \u03b2-chain (HLA-DPGlu69), can bind Be directly and present it to interferon (IFN)-\u03b3 releasing Th1 T-cell clones from patients with berylliosis; and 2) the cytokine gene tumour necrosis factor (TNF)-\u03b1 which has been shown to increase berylliosis risk independent of HLA-DPGlu69.<\/jats:p><jats:p>In order to determine whether TNF-\u03b1 release was triggered by Th1 T-cell activation by Be stimulation in the context of HLA-DPGlu69 molecules, the proliferation of BeSO<jats:sub>4<\/jats:sub>-stimulated blood mononuclear cells and the release of IFN-\u03b3, TNF-\u03b1, RANTES (regulated on activation normal T-cell expressed and secreted), granulocyte-macrophage colony-stimulating factor, interleukin (IL)-4, IL-6, IL-8, IL-10 and IL-12 by BeSO<jats:sub>4<\/jats:sub>-stimulated blood mononuclear cells was quantified in 11 individuals with berylliosis using an anti-HLA-DP antibody as a probe for HLA-DP restricted T-cell activation.<\/jats:p><jats:p>While proliferation and IFN-\u03b3 release were completely abrogated by HLA-DP inhibition (inhibition with anti-HLA-DP monoclonal antibody (mAb): 88\u00b116 and 77\u00b116%, respectively; anti-HLA-DR: 29\u00b138 and 14\u00b110%, respectively), the release of TNF-\u03b1 was not (inhibition with anti-HLA-DP mAb: 8.9\u00b17.8%). No other cytokine was detected at significant levels. Moreover, Be was able to induce TNF-\u03b1 production in healthy control subjects not exposed to Be in the absence of T-cell proliferation and IFN-\u03b3 production.<\/jats:p><jats:p>In conclusion, these data suggest that the tumour necrosis factor-\u03b1 response of mononuclear cells is independent of the activation of beryllium-specific human leucocyte anitgen-DP restricted T-cells, which is consistent with the finding that the tumour necrosis factorA2 and the human leucocyte anitgen-DPGlu69 genetic markers are independently interacting in increasing berylliosis risk.<\/jats:p>","DOI":"10.1183\/09031936.02.02232001","type":"journal-article","created":{"date-parts":[[2002,11,8]],"date-time":"2002-11-08T00:31:11Z","timestamp":1036715471000},"page":"1174-1178","source":"Crossref","is-referenced-by-count":24,"title":["HLA-DP-unrestricted TNF-\u03b1 release in beryllium-stimulated peripheral blood mononuclear cells"],"prefix":"10.1183","volume":"20","author":[{"given":"M.","family":"Amicosante","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.","family":"Berretta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Franchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Rogliani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Dotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Losi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Dweik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Saltini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"81","published-online":{"date-parts":[[2002,11,1]]},"reference":[{"key":"2024101809543955000_20.5.1174.1","unstructured":"Saltini C, Markham TN, Jones Williams W. 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