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

Important note: Information in this article was accurate in 1995. The state of the art may have changed since the publication date.

J Immunol. 1995 Mar 15;154(6):2928-38. Unique Identifier : AIDSLINE MED/95181808
Agostini C; Zambello R; Trentin L; Cerutti A; Enthammer C; Facco M; Milani A; Sancetta R; Garbisa S; Semenzato G; Padua University School of Medicine, Department of Clinical; Medicine, Italy.

Abstract: High amounts of TNF-alpha 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-alpha (TNF-Rs) and the presence of the transmembrane form of TNF-alpha (mTNF-alpha) on bronchoalveolar lavage (BAL) cells recovered from 14 patients with HIV-1 infection. The role of TNF-alpha 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 (CD120a) 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-alpha; when T cells were tested for their proliferative capacity, an up-regulation of the IL-2-mediated proliferation by TNF-alpha 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-alpha Ab, mTNF-alpha 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-alpha on cells accumulating within the alveolar spaces of patients with HIV-1 infection, pointing to the compound role of TNF-alpha in the local immune responses.

Keywords: Adult Cells, Cultured Cytotoxicity, Immunologic/IMMUNOLOGY Female Flow Cytometry Human HIV Infections/*IMMUNOLOGY HIV-1 Lung/IMMUNOLOGY Lymphocyte Transformation/IMMUNOLOGY Macrophages, Alveolar/*IMMUNOLOGY Male Precipitin Tests Receptors, Tumor Necrosis Factor/*ANALYSIS Support, Non-U.S. Gov't T-Lymphocytes/*IMMUNOLOGY Tumor Necrosis Factor/*ANALYSIS JOURNAL ARTICLE
950630
M9560851

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