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.
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.
Agostini
C
C
Padua University School of Medicine, Department of Clinical Medicine, Italy.
Zambello
R
R
Trentin
L
L
Cerutti
A
A
Enthammer
C
C
Facco
M
M
Milani
A
A
Sancetta
R
R
Garbisa
S
S
Semenzato
G
G
D000328:Adult; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D008168:Lung / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology*; D008297:Male; D011233:Precipitin Tests; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha