CD8+CD57+ T cells, expanded in peripheral blood lymphocytes of AIDS patients, inhibit the effector phase of HLA-specific cytotoxic T lymphocytes, natural killer and lymphocyte-activated killer cells in a 4-h chromium-release assay. This inhibitory activity present in supernatants of purified sorted CD8+CD57+ cells is mediated by a non-antigen-specific inhibitory factor which is distinct from prostaglandin E2, T cell growth factor (TGF)-beta, latent-TGF-beta, tumor necrosis factor (TNF)-alpha and TNF-beta. Partial biochemical characterization demonstrates that the CD8+CD57+ inhibitory activity (a) is heat, trypsin and acid resistant, (b) binds to concanavalin A columns, indicating its glycosylation state and (c) is mediated by a 20-30-kDa soluble molecule.
Late-onset interstitial pneumonitis following allogeneic bone marrow transplantation (BMT) is a rare condition usually caused by a variety of infective agents, although in some cases these are idiopathic. We investigated noninfectious late interstitial pneumonitis with lymphocytic alveolitis in seven allogeneic BMT recipients using bronchoalveolar lavage (BAL), lymphocyte phenotyping analysis, CT lung scans, and pulmonary function tests. The results were compared with those of a control group composed of similar patients with no pulmonary symptoms. Of 65 long-term survivors, seven were included in the study. All had chronic graft-versus-host disease (GVHD) and developed interstitial pneumonitis a median of 210 d (range 120 to 445 d) after BMT. BAL revealed lymphocytosis, with an overall expansion of CD8+ subsets (38 to 90%). Lymphocytic alveolitis was not observed in the control group. Pulmonary function tests revealed a restrictive syndrome, and biopsy samples obtained from 2 patients showed interstitial lymphoid infiltration with fibrosis of the alveolar walls. Of the 7 patients, six were cured by starting immunosuppressive drugs or increasing the dosage with a drastic improvement in respiratory symptoms within 1 mo. These findings suggest that CD8+ alveolitis may be observed in late interstitial pneumonitis in allogeneic BMT recipients and may be a pulmonary manifestation of chronic GVHD.
HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection or tumor. In some of them a fraction of alveolar lymphocytes are HIV-specific cytotoxic T-lymphocytes (CTL) bearing the CD8 and D44 cell surface markers and capable of killing HIV-infected alveolar macrophages. In order to evaluate the in vivo effect of these CTL on lung function, we measured the pulmonary clearance of aerosolized 99mTc-diethylene triamine penta-acetate (DTPA-CI) on 24 occasions in 22 patients with lymphocytic alveolitis. DTPA-CI has been selected as a highly sensitive test to detect injury of the lung epithelium. In 13 of the patients, we found a high DTPA-CI of 4.56 +/- 2.54%.min-1 (mean +/- SD), suggesting an increase of the epithelial permeability. The lymphocytic alveolitis was then characterized by a high cellularity, a high proportion of lymphocytes (59 +/- 18%), mainly composed of CD8+D44+ T-lymphocytes (149 +/- 109 cells/mm3), which spontaneously exhibited a cytolytic activity against the autologous alveolar macrophages in a standard 51Cr release assay. In the remaining 11 patients, DTPA-CI was normal (less than 1.78%.min-1), lymphocytic alveolitis being characterized by a low number or an absence of CD8+D44+ alveolar lymphocytes (9 +/- 13 cells/mm3) with no significant cytolytic activity. In the whole group, a significant correlation (r = 0.74, p = 0.0004) was found between the DTPA-CI and the number of CD8+D44+ lymphocytes and their cytotoxic activity against alveolar macrophages. Altogether, these results suggest that an injury of the lung epithelium could result from a HIV-specific CTL-induced immunologic conflict.
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