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 β-chain (HLA-DPGlu69), can bind Be directly and present it to interferon (IFN)-γ releasing Th1 T-cell clones from patients with berylliosis; and 2) the cytokine gene tumour necrosis factor (TNF)-α which has been shown to increase berylliosis risk independent of HLA-DPGlu69.

In order to determine whether TNF-α release was triggered by Th1 T-cell activation by Be stimulation in the context of HLA-DPGlu69 molecules, the proliferation of BeSO₄-stimulated blood mononuclear cells and the release of IFN-γ, TNF-α, 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 BeSO₄-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.

While proliferation and IFN-γ release were completely abrogated by HLA-DP inhibition (inhibition with anti-HLA-DP monoclonal antibody (mAb): 88±16 and 77±16%, respectively; anti-HLA-DR: 29±38 and 14±10%, respectively), the release of TNF-α was not (inhibition with anti-HLA-DP mAb: 8.9±7.8%). No other cytokine was detected at significant levels. Moreover, Be was able to induce TNF-α production in healthy control subjects not exposed to Be in the absence of T-cell proliferation and IFN-γ production.

In conclusion, these data suggest that the tumour necrosis factor-α 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.