Expression of TNF receptors by T cells and membrane TNF-α by alveolar macrophages suggests a role for TNF-α in the regulation of the local immune responses in the lung of HIV-1-infected patients

High amounts of TNF-α are released by alveolar macrophages (AMs) in the lungs of patients with HIV-1 infection. To investigate the role of this cytokine in the local immune response, we studied the expression of surface receptors for TNF-α (TNF-Rs) and the presence of the transmembrane form of TNF-α (mTNF-α) on bronchoalveolar lavage (BAL) cells recovered from 14 patients with HIV-1 infection. The role of TNF-α both in the events leading to the T cell alveolitis and as a mediator of cytotoxicity was also evaluated. TNF-R expression was determined by flow cytometry on BAL CD8 lymphocytes and AMs (i.e., the cells that account for the alveolitis in HIV-1 infection). We found that CD8 cells express the 75-kDa (CD120b) but not the 55-kDa (CD120a) TNF-Rs, whereas AMs were devoid of TNF-R expression. More than 90% of BAL T cells efficiently bound TNF-α; when T cells were tested for their proliferative capacity, an up-regulation of the IL-2-mediated proliferation by TNF-α was observed, suggesting that this cytokine may drive the in situ proliferation of CD120b⁺ T cells. As shown by flow cytometry analysis and immunoprecipitation with anti-TNF-α Ab, mTNF-α expression was observed on AMs but not on alveolar T cells. Fixed AMs showed high levels of killing against TNF-sensitive targets. Taken together, our data demonstrate the selective expression of TNF-Rs and mTNF-α on cells accumulating within the alveolar spaces of patients with HIV-1 infection, pointing to the compound role of TNF-α in the local immune responses.