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B Autran

Publications and source records attributed to B Autran.

47 records · Page 3Linked to original sources
PubMed1987

A T chronic lymphocytic leukemia with large granular lymphocytes. Phenotype and functions of leukemic cells under in vitro treatment by differentiation inducers.

We reported the morphologic, phenotypic and functional characteristics of leukemic cells with natural killer (NK) properties in a case of T chronic lymphocytic leukemia with large granular lymphocytes. These cells were cytologically and cytochemically characterized as phosphatase acid positive large granular lymphocytes (LGL), and presented parallel tubular arrays at the ultra structural level. They displayed a CD2, CD3, CD8, CD11, Leu 7, and Leu 11 positive phenotype while they lacked B cell markers including surface immunoglobulins. In addition, they expressed human leukocyte antigens (HLA) Class I, but no Class II antigens. These phenotypic studies were also performed after cells were cultured in vitro with 12-0-tetradecanoyl phorbol 13-acetate, gamma interferon, 5-azacytidine, sodium butyrate, phytohemagglutinin, and interleukin 2 (IL2). The cell surface markers underwent several significant changes. Among them we noted a higher percentage of labeled cells with anti-CD6 and CD7 monoclonal antibodies (moAbs), and a positivity with an anti-CD19 (B4) moAb. The leukemic LGL spontaneously developed a NK activity on K 562 tumor cells, which was not affected under the various T and B cells growth factors because they became more sensitive to IL2; but they were also stimulated by a 50-kilodalton (KD) B cell growth factor (BCGF) factor devoid of any T cell proliferation activity. Together these results gave a better characterization of azurophilic granules containing T chronic lymphocytic leukemia, and enabled the documentation of the differentiation of LGL with NK activity.

Adult↗
PubMed1987

Monoclonal B-cell response to diphtheria toxoid: evidence for cross-reactive epitopes.

Our previous studies on the human specific B- and T-cell responses against diphtheria toxoid (DT) had shown that the B- and T-cell antigenic determinants were mostly assembled topographic sites with large intra-molecular cross-reactivities. In order to characterize further the B-cell responses against DT, and to investigate these cross-reactivities, we have produced 54 murine monoclonal antibodies (moAbs) against the native DT. Determination of their antigenic specificity showed that 25 moAbs recognized conformational determinants on the native DT, 20 moAbs reacted against the A fragment (DTA) of the toxin, and nine moAbs reacted with at least three distinct highly purified CNBr peptides of the B fragment (DTB); some of them simultaneously recognized two or three purified CNBr peptides of DTB. As shown by cross-inhibition studies, the epitopes cross-reacting with those moAbs were distinct. Previously described sequence data indicated that these epitopes were not induced by repetitive amino-acid sequences. Finally, a cross-reactive idiotype was shared by moAbs specific for the CB1 and the CB3 peptides of DTB. Altogether, these data indicate that anti-DT moAbs are mostly directed against conformational determinants, and may cross-react with several DTB CNBr peptides.

Animals↗
PubMed1987

T-cell depletion of bone marrow transplants: assessment of standard immunological methods of quantification.

The efficacy of bone marrow transplant (BMT) T-cell depletion for the prevention of acute graft-versus-host disease (GVHD) has been demonstrated in animal models and in clinical studies. The importance of T-cell depletion has to be evaluated with standardized methods suitable for routine purposes. We report herein an in vitro mature T-cell depletion using a cocktail of three monoclonal antibodies (CD2, CD5, and CD7) and baby rabbit complement in 38 histocompatibility leucocyte antigen (HLA)-identical BMT with no more than grade II acute GVHD. The T-cell depletion was quantified using three prestandardized immunological methods: immunofluorescence (IF) analysis, SRBC-rosetting assay, and PHA proliferation assay. A mean of 97.5% IF-assessed T-cell depletion was achieved in the 38 BMT. The immediate IF analysis using three distinct sets of anti-T-cell monoclonal antibodies allowed us to detect a mean of 1.2% residual T cells. The SRBC-rosetting assay was not useful to quantify T-cell depletion because no residual SRBC-rosette-forming cells could be detected in every case. The results of a prestandardized PHA-induced proliferation assay gave a mean 96.7% inhibition of proliferation, and they were correlated with the IF results although the IF threshold of detection was higher. From these data we conclude that our in vitro T-cell-depletion procedure is reproducible and that standardized simple immunological methods such as immediate immunofluorescence analysis and PHA proliferation assay provide good tools to assess a T-cell depletion effective in the prevention of acute GVHD.

Adolescent↗
PubMed1986

Immune response to diphtheria toxin and to different CNBr fragments: evidence for different B and T cell reactivities.

The antigenic structure of the diphtheria toxin has been studied in man. B and T cell responses to diphtheria toxoid and to different fragments of the toxin molecule were analyzed in 4 individuals one month after booster immunization. Studies on the B cell response showed that: part of the response was directed against assembled topographic sites; 80% of the response was directed against determinants present on fragment A; the few determinants present on the CNBr peptides of B cross-react with determinants present on A; and reduction of the second disulfide bridge of fragment B diminishes the response. In contrast to the antibody response, most of the T cell reactivity was directed against the B fragment or CNBr peptides from this fragment. Analysis of the fine specificity of T lymphocyte clones revealed that some CNBr fragments share common T cell determinants. These studies indicate that T and B cell determinants are differently distributed on the molecule and that large cross-reactivities that are not explained by the analysis of the amino acid sequence could be found at the B and T cell level.

Antibody Formation↗
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

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↗