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B Autran

Publications and source records attributed to B Autran.

162 records · Page 9Linked to original sources
PubMed1984

Antigen-specific proliferative human T cell clones with specificity for diphtheria toxoid: genetic and molecular restriction by class II antigens.

Human T lymphocyte clones (TLC) specific for diphtheria toxoid (DT) were isolated from a DR6/7 individual by cloning in soft agar in vivo sensitized T lymphocytes. We report here the isolation and characterization of 3 of these clones by studying: (a) the kinetic of activation, (b) the surface phenotypes, (c) the fine specificity for one of the 2 DT chains and (d) the genetic restriction of the proliferative response by the haplotype DR7. Moreover, blocking studies of the proliferative response to DT by various immunochemically characterized anti-HLA-DR monoclonal antibodies indicate that, on the DR7 molecule, more than one Ia determinant may participate in the clonal DT proliferative response. By using human TLC of a defined specificity and well-characterized anti-DR monoclonal antibodies, such studies may help to define the functional repertoire of Ia molecules in man.

Clone Cells↗
PubMed1981

[Pancreatic cancer revealed by hyperosmolar coma: report on two cases (author's transl)].

Hyperosmolar diabetic coma revealed the presence of a pancreatic cancer in two patients. The first case was a 59-year-old man, without a history of diabetes, treated with prednisone for jaundice and marked weight loss over the last month, and admitted in hyperosmolar coma (346 m0sm/l). After recovery from the acute episode, a diagnosis of adenocarcinoma of the head of the pancreas was established following operation. The patient died six months later. The second case, a 71-year-old man also without a history of diabetes, was admitted in hyperosmolar coma (315 m0sm/l) during the course of a pulmonary infection. Rapidly fatal cholostatic jaundice appeared one year later. An adenocarcinoma of the head of the pancreas was demonstrated at autopsy. The diagnostic criteria in both cases were those of hyperosmolar diabetic coma. Though cases of combined diabetes and pancreatic cancer are well documented, only one case of hyperosmolar coma and cancer of the pancreas has been reported in the published literature. The pathogenesis of hyperosmolar diabetic coma is discussed. The fact that it developed during the course of a pancreatic affection could be explained by a functional reduction in insulin secretion, associated with a triggering factor such as dehydration, infection, hypoglycemic agent administration, etc... The onset of hyperosmolar diabetic coma in an elderly patient without a history of diabetes, especially with associated marked weight loss, should lead to investigation for a possible pancreatic cancer.

Adenocarcinoma↗
PubMedDate not supplied

HIV-specific cytotoxic T lymphocytes directed against alveolar macrophages in HIV-infected patients.

A CD8+ lymphocytic infiltration of the lungs is frequently observed in HIV-infected patients, even prior to the onset of opportunistic infections. In such patients, we could demonstrate that most of these CD8+ alveolar T lymphocytes displayed the D44 marker and were functional cytolytic T lymphocytes directed against autologous HIV-infected alveolar macrophages. This primary cytolytic activity was HLA-restricted and, at least partially, specific for the HIV envelope protein, since HLA-A2 alveolar T lymphocytes could specifically lyse cell lines expressing both the HLA-A2 and Env antigens. In contrast to data obtained in peripheral blood, no ADCC activity was observed against the Env antigen. HIV-specific alveolar T-lymphocyte cytolytic activity decreased with progression towards AIDS as shown by studies of a series of 40 patients. Functional abnormalities of the lung epithelium could be associated with the specific lysis of alveolar macrophages, suggesting that local tissue injury could result from the in vivo immune conflict between alveolar HIV-specific CTL and HIV-infected macrophages.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

HIV-specific cytotoxic T lymphocytes against alveolar macrophages: specificities and downregulation.

To analyse the evolution of alveolar-lymphocyte-mediated cytotoxic activity directed against autologous alveolar macrophages (AM), cytotoxic assays against various HIV+ target cells were performed in a cohort of 75 patients with HIV-associated lymphoid interstitial pneumonitis (LIP) studied at distinct stages of HIV infection. Our data confirm that alveolar HIV-specific cytotoxic T lymphocytes (CTL) against AM were detectable before AIDS in patients with CD8+ LIP. Mild CD8+ lymphocytic alveolitis occurs silently in 62% of stage II and III patients with no respiratory symptoms. In these cases, the lack of spontaneous alveolar-lymphocyte-mediated cytotoxic activity against autologous AM may contrast with the detection of primary alveolar CTL specific for HIV proteins such as nef. In AIDS patients, the alveolar CTL lytic efficiency against both AM- and HIV-antigen-expressing cells can be inhibited by a suppressor factor produced by alveolar CD8+ CD57+ cells. Therefore, spontaneous CTL lysis of AM may be (1) limited to a subgroup of patients with active LIP and (2) controlled by distinct mechanisms, including suppressor phenomenons, and HIV replication levels in AM.

Cohort Studies↗
PubMedDate not supplied

Low infection frequency of macrophages in the spleens of HIV+ patients.

Macrophages are often considered as a reservoir of latent infection in HIV+ patients, and their infection may indeed be very important functionally. However, some quantitative studies did not find high infection frequencies in peripheral blood monocytes. Since lymphoid organs are the major site of infection, macrophage infection was tested in spleens removed from HIV+ patients for treatment of different syndromes. Ten replicates of limiting dilutions from different cell populations were submitted to a nested PCR specific to conserved regions of HIV1 env DNA. On an average, 1/2,300 adherent cells carried HIV1 DNA (n = 7; range: 1/55,000 to 1/660). These adherent cells, obtained after two days of culture, comprised the whole macrophage population, with no biases introduced by surface molecule selection, but were not pure (41-78% macrophages). Only 1/37,000 CD14+ monocyte/macrophages were positive (n = 6; range: 1/130,000 to 1/22,000). Therefore, the infection frequency of the isolated splenic monocytes/macrophages from these patients could be estimated at between 1/37,000 and 1/2,300. In contrast, 1/60 CD4+ T lymphocytes were positive (n = 7; range: 1/190 to 1/17). Within the experimental limits, such as cell isolation, required for accurate quantification, this study in the spleen indicates, as have other studies on peripheral blood, that macrophages do not quantitatively constitute an important reservoir of HIV when compared to CD4+ T lymphocytes.

CD4-Positive T-Lymphocytes↗
PubMedDate not supplied

Dose-dependent systemic human immunodeficiency virus infection of SCID-hu mice after intraperitoneal virus injection.

SCID mice were engrafted with human foetal liver, thymus and lung. Human cells were subsequently detected among peripheral blood leukocytes for 81% of tested animals and in tissue implants for 100% of tested animals. SCID-hu mice received intraperitoneal injections of human immunodeficiency virus type 1 (HIV1) at from 20 up to 20,000 median tissue culture infectious doses (TCID5). HIV1 infection was detected by means of cell culture and polymerase chain reaction both in blood and implants, up to 58 days after infection. The rate of infection was dependent upon the inoculated dose: the frequency of thymus infection ranged from 14% with 20-500 TCID50 up to 100% with 20,000 TCID50. HIV1 infection was detected less frequently in blood leukocytes than in thymus. Thymus virus load ranged from 40 to 50,000 HIV1 provirus copies per million cells and was not correlated with either infectious dose or viraemia. Thymus T-cell depletion was observed mainly in the CD1+4+8+ immature thymocyte compartment. The same rate of SCID-hu mouse infection was obtained using three different primary HIV1 isolates, suggesting that infection was not restricted to a few particular virus strains. The systemic infection of SCID-hu mice following intraperitoneal virus injection mimics some traits of human HIV infection and provides a promising, novel approach for future investigations in this field.

Animals↗
PubMedDate not supplied

AIDS virus-specific cytotoxic T lymphocytes in lung disorders.

Human immunodeficiency virus (HIV) is implicated in the development of AIDS (acquired immune deficiency syndrome). HIV infection leads to the generation of HIV-specific thymus-derived (T) lymphocytes in humans and apes. We describe an experimental system permitting the quantitative and systematic analysis of HIV-specific cytotoxic T lymphocytes (CTL). Functional, HIV-specific CTL are obtained by broncho-alveolar lavage (BAL) from the lungs of seropositive patients with lymphocytic alveolitis. These alveolar CTL: (1) recognize and kill HIV-infected alveolar macrophages in vitro under autologous, but not heterologous, conditions; (2) correspond to standard CTL as they express the CD3 and CD8 surface markers, but not the CD4 marker; and (3) are restricted by class I HLA transplantation antigens in their cytotoxic activities. We propose the hypothesis that interactions between HIV-specific CTL and infected macrophages induce major inflammatory reactions in seropositive patients.

Cytotoxicity, Immunologic↗
PubMedDate not supplied

[Acute cardiac graft rejection after orthotopic cardiac transplantation. Elements of diagnosis and monitoring, therapeutic attitude].

The diagnosis of acute rejection in heart allograft recipients receiving cyclosporine is still an important challenge. The poor diagnostic value of clinical signs and the ECG means that regular endomyocardial biopsies must be performed. Despite their diagnostic value during the first year after transplantation, endomyocardial biopsies are less sensitive there after and currently suffer from the lack of a universally accepted histological classification. Doppler echocardiography can be used for routine surveillance and has proven reliable for the diagnosis of acute rejection with various clinical presentations when used in conjunction with endomyocardial biopsies. Immunohistological examination of myocardial specimens can further increase the sensitivity of histological diagnosis. Similarly, immunoscintigraphy with indium 111-labelled antimyosin antibodies is of value for the prediction of acute rejection after the first year. Therapeutic approaches have been standardized, but must still be tailored to the individual patient according to the severity of the rejection and the presence of associated infection and/or metabolic disturbances.

Acute Disease↗
PubMedDate not supplied

[Anti-I anti-erythrocyte auto-immunization in malaria].

An anti-erythrocyte autoimmunization with anti-I specificity was shown in patients previously exposed to malaria (falciparum malaria in 98.7% of cases). An anti-I antibody was eluted from red cells in 14.6% of 41 patients with an acute P. falciparum infection. The frequency of the anti-I immunisation was found to be correlated to the rate of the antimalarial antibodies among the 152 patients without parasitaemia, coming from areas endemic for falciparum malaria: this frequency was 5.2% for a rate below 1/64, 9.7% for a rate between 1/64 and 1/256, and 34% for a rate above 1/1,024. Anti-I antibodies were more often noted in African patients coming from forest areas, considered as chronically infected with P. falciparum, and in other patients who have been in France for less than a month. No anti-I antibodies were found in the control group, composed of 52 Caucasian healthy subjects with no previous exposure to malaria. This anti-I immunisation was transitory and its disappearance was usually accompanied by a lowering of anti-malarial antibodies.

Africa, Northern↗
PubMedDate not supplied

Imbalanced "memory" T lymphocyte subsets and analysis of dendritic cell precursors in the peripheral blood of adult patients with Langerhans cell histiocytosis.

OBJECTIVES: To investigate the phenotype of lymphocytes and dendritic cell precursors in the peripheral blood of adult patients with histiocytosis X. METHODS: Data were obtained on patients with histiocytosis X treated in La Pitié-Salpetrière Hospital. Peripheral blood mononuclear cells from 10 patients (4 with unifocal and 6 with disseminated disease) were studied by flow cytometry. A method was set up to detect circulating Langerhans cells, dendritic cells and their precursors. RESULTS: An abnormal repartition of "memory" T lymphocyte subsets was observed, with a significant decrease of CD4CD45RO and CD8CD45RO and a reciprocal increase of CD4CD45RA "naive" cells, while CD4+ cells displaying the accessory molecule CD28 were decreased in some patients. These abnormalities disappeared in vitro after triggering of the CD3 and CD28 molecules in the absence of antigen presenting cells, hence demonstrating that there was no constitutive defect in the capacity of CD4+ and CD8+ T cells to convert from the CD45RO- to the CD45RO+ isoform. Langerhans cells were undetectable in the peripheral blood, and dendritic cells and their precursors were present in normal proportions (0.5 +/- 0.2% and 2.8 +/- 1.2%, respectively), but the latter were more numerous (4% and 6% of the PBMC) in the two patients with the more severe form of the disease. CONCLUSIONS: We found in these patients some T lymphocyte phenotype abnormalities which suggest alterations in antigen-driven activation processes. The number of dendritic precursor cells was not consistently elevated in the peripheral blood from histiocytosis X patients.

Adult↗