Jean-Marcel Guillon - Academia.edu (original) (raw)
Papers by Jean-Marcel Guillon
The American review of respiratory disease, Sep 16, 1988
PubMed, 1992
We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance meas... more We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance measurements with those of fiberoptic bronchoscopy in 88 patients infected with the human immunodeficiency virus. Of 100 investigations, a pulmonary infection was diagnosed in 39, mainly Pneumocystis carinii pneumonia and a noninfectious disorder was found in 42, mainly Kaposi's sarcoma and lymphocytic alveolitis. Gallium scans and DTPA clearance were abnormal respectively in 74% and 92% of infectious complications, and in 12% and 60% of noninfectious disorders. In 10 cases, DTPA clearance was accelerated, while chest x-ray, arterial blood gases and even gallium scanning were normal. A value of DTPA clearance greater than 4.5%.min-1 was both sensitive and specific for the diagnosis of Pneumocystis carinii pneumonia. The gallium scan was always normal in bronchopulmonary Kaposi's sarcoma. We conclude that in symptomatic patients: (1) DTPA clearance measurements are useful for detecting lung disease when chest x-ray and/or PaO2 are normal and (2) a gallium scan is indicated to distinguish progressive Kaposi's sarcoma from a superimposed second process when radiological abnormalities of pulmonary Kaposi's sarcoma are present.
Annals of Internal Medicine, Sep 15, 1992
To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Case s... more To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Case study. Intensive care unit of a referral hospital. A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. Immunologic analysis of the phenotype and function of alveolar lymphocytes. Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.
Research in Virology, Mar 1, 1990
American Journal of Respiratory and Critical Care Medicine, Oct 1, 1994
Late-onset interstitial pneumonitis following allogeneic bone marrow transplantation (BMT) is a r... more 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.
Research in Immunology, 1989
Journal of Immunology, Oct 1, 1989
Rapidly expanded activated human killer cell clones have strong antitumor cell activity and have ... more Rapidly expanded activated human killer cell clones have strong antitumor cell activity and have the surface phenotype of either T gamma, T-non-gamma, or null cells.
The American review of respiratory disease, May 1, 1990
HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection ... more 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.
Research in Virology, 1991
... Young et al., 1985. KR Young, JA Rankin, GP Naeger, ES Paul and HY Reynolds , Bronchoalveolar... more ... Young et al., 1985. KR Young, JA Rankin, GP Naeger, ES Paul and HY Reynolds , Bronchoalveolar lavage cells and proteins in patients with the acquired immunodeficiency syndrome. Ann. intern. Med. 103 (1985), pp. 522533. View Record in Scopus | Cited By in Scopus ...
The American Journal of Medicine, 1987
American Journal of Respiratory and Critical Care Medicine, 1994
Late-onset interstitial pneumonitis following allogeneic bone marrow transplantation (BMT) is a r... more 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.
European Journal of Immunology, 1989
Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice* The human immunod... more Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice* The human immunodeficiency virus type 1 (HIV-1) induces a strong cytotoxic T lymphocyte (CTL) response in humans following infection. HIV-specific CTL can be detected directly in the blood and lungs of infected patients, and can be expanded in vitro by stimulation with autologous HIV-infected lymphoblasts. Furthermore, CTL specific for HIV envelope glycoprotein gp160 have been obtained in mice by immunization with recombinant vaccinia virus (VV) that carry the HIV env gene. In this study, we show that mice also produce strong CTL responses to gag and nef proteins following immunization with W recombinants, thus providing a convenient model system to study T lymphocyte immunity to defined HIV antigens. To determine the specificity of circulating HIV-immune CTL in humans, a panel of doubly transfected mouse P815 tumor cells was produced which express the human HLA-A2 or HLA-A3 transplantation antigen gene and one HIV-1 gene (env, gag or nef). Using these cells as targets to CTL, we show that HIV-infected humans carry co-existing CTL subpopulations of different specificities. Each subpopulation appears to vary in intensity among different individuals. Surprisingly, CTL specific for regulatory, non-structural nef protein appear to be a major constituent of the human immune response to HIV.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1992
We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance meas... more We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance measurements with those of fiberoptic bronchoscopy in 88 patients infected with the human immunodeficiency virus. Of 100 investigations, a pulmonary infection was diagnosed in 39, mainly Pneumocystis carinii pneumonia and a noninfectious disorder was found in 42, mainly Kaposi's sarcoma and lymphocytic alveolitis. Gallium scans and DTPA clearance were abnormal respectively in 74% and 92% of infectious complications, and in 12% and 60% of noninfectious disorders. In 10 cases, DTPA clearance was accelerated, while chest x-ray, arterial blood gases and even gallium scanning were normal. A value of DTPA clearance greater than 4.5%.min-1 was both sensitive and specific for the diagnosis of Pneumocystis carinii pneumonia. The gallium scan was always normal in bronchopulmonary Kaposi's sarcoma. We conclude that in symptomatic patients: (1) DTPA clearance measurements are useful for detectin...
The American journal of …, 1993
PURPOSE To evaluate the long-term effkacy and safety of inhaled pentamidine as primary prophylaxi... more PURPOSE To evaluate the long-term effkacy and safety of inhaled pentamidine as primary prophylaxis against Pneumocystis ca.riG pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV). PATIENTS Two hundred thirty-two HIV-infected patients with a CD4 cell count below 20% of the total lymphocyte couut were given aerosolized pen-0 once every 4 weeks for more than 3 months. Pentamidine aerosols were administered at the hospital under medical supervision. Prevention of bronchospasm was carried out us.& inhaled salbutamol. RESULTS Mean duration of prophylaxis was 16.9 months. Eleven patienta (4.7%; [95% confidence interval 2 % to 7.4 % 1) developed PCP. Probability to remain free of PCP is 96.6% at 12 months, 94% at 18 months, and 88% at 24 months. Mean delay between the ouset of the prophylaxis and the occurrence of PCP for the 11 patienta was 12.9 months (range: 4 to 26 months). No major side effect was observed, and minor side effects (cough, acute dyspnea) were infrequent. CONCLUBION: The efficacy and tolerance of aerosolkd pentamidiue as shown in our study support its use as primary prophylaxis against I? cariaii in HIV-infected patients. From the Department of Chest Medicine (SP. JMG, A Belguendouz, JL). Deoarbnent of Internal Madiclne (D Salmon, FR. ET. MER. D Ward. D&e& A Boissonnas). Department of Dermatology (JD. JPM, IG). and Hemophilia Center (JMB. DB. YS). Hopital Cochin,
American Review of Respiratory Disease, 1990
HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection ... more 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.
European Journal of Immunology, 1991
CD8+CD57+ T cells, expanded in peripheral blood lymphocytes of AIDS patients, inhibit the effecto... more 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.
Annals of Internal Medicine, 1992
To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Case s... more To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Case study. Intensive care unit of a referral hospital. A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. Immunologic analysis of the phenotype and function of alveolar lymphocytes. Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.
The American review of respiratory disease, Sep 16, 1988
PubMed, 1992
We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance meas... more We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance measurements with those of fiberoptic bronchoscopy in 88 patients infected with the human immunodeficiency virus. Of 100 investigations, a pulmonary infection was diagnosed in 39, mainly Pneumocystis carinii pneumonia and a noninfectious disorder was found in 42, mainly Kaposi's sarcoma and lymphocytic alveolitis. Gallium scans and DTPA clearance were abnormal respectively in 74% and 92% of infectious complications, and in 12% and 60% of noninfectious disorders. In 10 cases, DTPA clearance was accelerated, while chest x-ray, arterial blood gases and even gallium scanning were normal. A value of DTPA clearance greater than 4.5%.min-1 was both sensitive and specific for the diagnosis of Pneumocystis carinii pneumonia. The gallium scan was always normal in bronchopulmonary Kaposi's sarcoma. We conclude that in symptomatic patients: (1) DTPA clearance measurements are useful for detecting lung disease when chest x-ray and/or PaO2 are normal and (2) a gallium scan is indicated to distinguish progressive Kaposi's sarcoma from a superimposed second process when radiological abnormalities of pulmonary Kaposi's sarcoma are present.
Annals of Internal Medicine, Sep 15, 1992
To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Case s... more To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Case study. Intensive care unit of a referral hospital. A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. Immunologic analysis of the phenotype and function of alveolar lymphocytes. Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.
Research in Virology, Mar 1, 1990
American Journal of Respiratory and Critical Care Medicine, Oct 1, 1994
Late-onset interstitial pneumonitis following allogeneic bone marrow transplantation (BMT) is a r... more 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.
Research in Immunology, 1989
Journal of Immunology, Oct 1, 1989
Rapidly expanded activated human killer cell clones have strong antitumor cell activity and have ... more Rapidly expanded activated human killer cell clones have strong antitumor cell activity and have the surface phenotype of either T gamma, T-non-gamma, or null cells.
The American review of respiratory disease, May 1, 1990
HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection ... more 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.
Research in Virology, 1991
... Young et al., 1985. KR Young, JA Rankin, GP Naeger, ES Paul and HY Reynolds , Bronchoalveolar... more ... Young et al., 1985. KR Young, JA Rankin, GP Naeger, ES Paul and HY Reynolds , Bronchoalveolar lavage cells and proteins in patients with the acquired immunodeficiency syndrome. Ann. intern. Med. 103 (1985), pp. 522533. View Record in Scopus | Cited By in Scopus ...
The American Journal of Medicine, 1987
American Journal of Respiratory and Critical Care Medicine, 1994
Late-onset interstitial pneumonitis following allogeneic bone marrow transplantation (BMT) is a r... more 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.
European Journal of Immunology, 1989
Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice* The human immunod... more Multiple subsets of HIV-specific cytotoxic T lymphocytes in humans and in mice* The human immunodeficiency virus type 1 (HIV-1) induces a strong cytotoxic T lymphocyte (CTL) response in humans following infection. HIV-specific CTL can be detected directly in the blood and lungs of infected patients, and can be expanded in vitro by stimulation with autologous HIV-infected lymphoblasts. Furthermore, CTL specific for HIV envelope glycoprotein gp160 have been obtained in mice by immunization with recombinant vaccinia virus (VV) that carry the HIV env gene. In this study, we show that mice also produce strong CTL responses to gag and nef proteins following immunization with W recombinants, thus providing a convenient model system to study T lymphocyte immunity to defined HIV antigens. To determine the specificity of circulating HIV-immune CTL in humans, a panel of doubly transfected mouse P815 tumor cells was produced which express the human HLA-A2 or HLA-A3 transplantation antigen gene and one HIV-1 gene (env, gag or nef). Using these cells as targets to CTL, we show that HIV-infected humans carry co-existing CTL subpopulations of different specificities. Each subpopulation appears to vary in intensity among different individuals. Surprisingly, CTL specific for regulatory, non-structural nef protein appear to be a major constituent of the human immune response to HIV.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 1992
We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance meas... more We retrospectively compared the results of 67Ga chest scans and 99mTc-DTPA aerosol clearance measurements with those of fiberoptic bronchoscopy in 88 patients infected with the human immunodeficiency virus. Of 100 investigations, a pulmonary infection was diagnosed in 39, mainly Pneumocystis carinii pneumonia and a noninfectious disorder was found in 42, mainly Kaposi's sarcoma and lymphocytic alveolitis. Gallium scans and DTPA clearance were abnormal respectively in 74% and 92% of infectious complications, and in 12% and 60% of noninfectious disorders. In 10 cases, DTPA clearance was accelerated, while chest x-ray, arterial blood gases and even gallium scanning were normal. A value of DTPA clearance greater than 4.5%.min-1 was both sensitive and specific for the diagnosis of Pneumocystis carinii pneumonia. The gallium scan was always normal in bronchopulmonary Kaposi's sarcoma. We conclude that in symptomatic patients: (1) DTPA clearance measurements are useful for detectin...
The American journal of …, 1993
PURPOSE To evaluate the long-term effkacy and safety of inhaled pentamidine as primary prophylaxi... more PURPOSE To evaluate the long-term effkacy and safety of inhaled pentamidine as primary prophylaxis against Pneumocystis ca.riG pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV). PATIENTS Two hundred thirty-two HIV-infected patients with a CD4 cell count below 20% of the total lymphocyte couut were given aerosolized pen-0 once every 4 weeks for more than 3 months. Pentamidine aerosols were administered at the hospital under medical supervision. Prevention of bronchospasm was carried out us.& inhaled salbutamol. RESULTS Mean duration of prophylaxis was 16.9 months. Eleven patienta (4.7%; [95% confidence interval 2 % to 7.4 % 1) developed PCP. Probability to remain free of PCP is 96.6% at 12 months, 94% at 18 months, and 88% at 24 months. Mean delay between the ouset of the prophylaxis and the occurrence of PCP for the 11 patienta was 12.9 months (range: 4 to 26 months). No major side effect was observed, and minor side effects (cough, acute dyspnea) were infrequent. CONCLUBION: The efficacy and tolerance of aerosolkd pentamidiue as shown in our study support its use as primary prophylaxis against I? cariaii in HIV-infected patients. From the Department of Chest Medicine (SP. JMG, A Belguendouz, JL). Deoarbnent of Internal Madiclne (D Salmon, FR. ET. MER. D Ward. D&e& A Boissonnas). Department of Dermatology (JD. JPM, IG). and Hemophilia Center (JMB. DB. YS). Hopital Cochin,
American Review of Respiratory Disease, 1990
HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection ... more 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.
European Journal of Immunology, 1991
CD8+CD57+ T cells, expanded in peripheral blood lymphocytes of AIDS patients, inhibit the effecto... more 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.
Annals of Internal Medicine, 1992
To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Case s... more To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. Case study. Intensive care unit of a referral hospital. A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. Immunologic analysis of the phenotype and function of alveolar lymphocytes. Reexposure to minocycline but not to amoxicillin was followed by an interstitial pneumonitis. Sequential bronchoalveolar lavages showed a transient rise of eosinophils and neutrophils and a persistent alveolar lymphocytosis. Alveolar lymphocytes consisted predominantly of CD8+ but also CD4+ cells. Two CD8+ lymphocyte subsets were identified: CD8+ D44+ cytotoxic T cells that increased rapidly after the drug was resumed and CD8+ CD57+ suppressor T cells that predominated 11 days after the drug's withdrawal. In-vitro assays showed the presence of a lymphocyte-mediated specific cytotoxicity against minocycline-bearing alveolar macrophages. These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.