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Biomedical subjects

B Autran

Publications and source records attributed to B Autran.

At least 109 records · Page 6Linked to original sources
PubMed1995

Infection frequency of dendritic cells and CD4+ T lymphocytes in spleens of human immunodeficiency virus-positive patients.

Dendritic cells (DC) are specialized antigen-presenting leukocytes that are responsible for the activation of naive as well as memory T lymphocytes. If infected by human immunodeficiency virus (HIV), DC may transfer virus to CD4+ lymphocytes. However, the question of whether DC are infected in vivo is controversial. As HIV infection is more active in secondary lymphoid organs than in blood, infection of splenic DC isolated from HIV-seropositive patients was investigated. Splenic DC were first enriched and characterized by flow cytometry from HIV- donors. After direct isolation, they were negative for monocyte and T- and B-lymphocyte markers, negative for CD1a, but positive for major histocompatibility complex class II and CD4. After in vitro maturation, major histocompatibility complex class II expression increased, while CD4 expression was lost. Extensive purification from the spleens of seven HIV+ patients was performed by fluorescence-activated cell sorting. The frequency of cells harboring HIV DNA in purified populations was quantified by limiting-dilution PCR. Directly isolated DC (average, 1/3,000; range, 1/720 to 1/18,000) were in each patient 10 to 100 times less infected than CD4+ T lymphocytes (average, 1/52; range, 1/17 to 1/190). On average, 1/1,450 (1/320 to 1/6,100) unseparated mononuclear splenocytes (containing 5% CD4+ lymphocytes) harbored HIV DNA. In conclusion, in these HIV+ patient spleens, DC seem to be infected, but HIV-DNA positive CD4+ T lymphocytes accounted for the vast majority of infected mononuclear splenocytes.

CD4-Positive T-Lymphocytes↗
PubMed1994

HIV and T cell expansion in splenic white pulps is accompanied by infiltration of HIV-specific cytotoxic T lymphocytes.

Human immunodeficiency virus (HIV) replication and T cell proliferation were investigated in situ by a PCR-based analysis of individual microdissected splenic white pulps. Founder effects, revealed by an exquisite compartmentalization of HIV genotypes and T cells, indicated the recruitment of latently infected CD4+ T cells through highly localized antigen presentation rather than the infection of CD4+ T lymphoblasts by blood-borne virus or immune complexes. HIV-infected white pulps could be infiltrated by HIV-specific cytotoxic T lymphocytes, thereby implicating them in CD4+ T cell destruction in vivo. Together these data describe an iterative and deleterious mechanism of antigen-driven T cell recruitment and activation, as well as HIV replication and spread, with consequent destruction of the newly infected cells.

Amino Acid Sequence↗
PubMed1994

Oligoclonal expansion of CD8+ CD57+ T cells with restricted T-cell receptor beta chain variability after bone marrow transplantation.

A major expansion of CD8+57+ lymphocytes expressing an alpha-beta T-cell receptor (TCR) is frequent after bone marrow transplantation (BMT). We examined the clonality of the TCR beta gene repertoire in these expanded CD8+57+ cells after allogeneic or autologous BMT. We performed a polymerase chain reaction (PCR) analysis of the V beta chain usage in CD8+57+ cells purified from nine BMT recipients with a series of oligonucleotides specific for 20 V beta gene families. PCR products from selected TCR beta gene rearrangements were sequenced. The CD8+57+ cells from eight of nine patients used a restricted set of V beta families, with a marked predominance of two to three V beta gene families per patient, whereas the control autologous CD57- subset expressed the whole 20 V beta families. A direct sequencing analysis confirmed the V beta 16 and V beta 17 clonality in six patients, showing a striking homology in the CDR3 sequences of the V beta 16 products. The CD8+57+ cells, but not the CD57- cells, displayed an oligoclonal pattern of TCR rearrangements as shown by PCR analysis of TCR gamma gene rearrangements. Such an oligoclonal expansion of CD8+57+ cells, using a restricted set of the V beta gene families, may result from a specific TCR stimulation of a limited number of T-cell clones in BMT recipients.

Amino Acid Sequence↗
PubMed1994

An inhibitor of cytotoxic functions produced by CD8+CD57+ T lymphocytes from patients suffering from AIDS and immunosuppressed bone marrow recipients.

An inhibitor of the cytotoxic functions (ICF) mediated by human immunodeficiency virus (HIV)- or HLA-specific cytotoxic T lymphocytes, natural killer and lymphokine-activated killer (LAK) cells is secreted by CD8+CD57+ T lymphocytes, a subset expanded during infection with HIV and after bone marrow transplantation. We previously showed an apparent molecular mass of 20-30 kDa for this soluble glycosylated concanavalin A-binding inhibitor which is distinct from known cytokines. Here, we report a characterization of the mechanism of action of this CD8+CD57+ ICF. We show that the ICF-induced inhibition of LAK cell cytolytic activity is transient, with a spontaneous recovery of cytolytic potential after 18 h. When testing interactions of ICF with a large set of cytokines we found that the ICF-mediated inhibition of cytotoxic functions is antagonized by two cytokines: recombinant interleukin (rIL)-4 and recombinant interferon (rIFN)-gamma. Finally, we show that ICF acts at the level of cytolytic effector cells, where it induces a significant increase of cyclic AMP (cAMP) level. In contrast, no modification of either cell surface antigen expression or of target/effector cell conjugate formation could be evidenced. Addition of rIL-4 and rIFN-gamma reverses such an increase of cAMP levels and in parallel restores the cytolytic activity. Altogether, these data demonstrate that the glycoprotein ICF produced by CD8+CD57+ cells (1) inhibits cell-mediated cytotoxicity by sensitizing cytolytic effector cells to the cAMP pathway, and (2) is part of a cytokine network controlling cell-mediated cytotoxic functions.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Profound and possibly primary "idiopathic CD4+ T lymphocytopenia" in a patient with fungal infections.

A profound and long-lasting reduction in circulating CD4+ T lymphocytes (< 80/microliters) was found in a 37-year-old man (without known risk factors for HIV infection) presenting with recurrent oral candidiasis who subsequently developed cryptococcal meningitis. Infection with HIV was ruled out by serological and virological studies. In vitro and in vivo cell-mediated immunity was severely impaired. Abnormal phenotypic patterns of both CD4+ and CD8+ cells were consistently observed. A systematic family survey revealed in some of his asymptomatic relatives several immunological abnormalities which may point to a genetically based primary immunodeficiency disorder.

Adult↗
PubMed1994

Alveolar CD8+CD57+ lymphocytes in human immunodeficiency virus infection produce an inhibitor of cytotoxic functions.

We investigated the CD8+CD57+ alveolar cell functions and their immunoregulatory role in lungs from HIV-seropositive patients with the clinical presentation of lymphocytic alveolitis at different stages of human immunodeficiency virus (HIV) disease. We previously reported, at Stage IV of HIV infection, an expansion of CD8+CD57+ alveolar lymphocytes mirroring the decline of local anti-HIV cytotoxic T-lymphocyte (CTL) responses, and demonstrated that sorted CD8+CD57+ alveolar lymphocytes inhibited the effector phase of these HIV-specific CTL. In the present study, we show that the expansion of CD8+CD57+ alveolar T cells can also be detected at stages II and III of HIV disease, although at a lower degree than observed at Stage IV of HIV infection. When sorted, these CD8+CD57+ alveolar lymphocytes block effector killer cells such as allospecific CTL, natural killer (NK), and lymphokine-activated killer (LAK) cells. The mechanism of action of these inhibitory T-lymphocytes has been further studied and we demonstrated that: (1) cell-to-cell contact between inhibitor and killer is not required, (2) nonstimulated alveolar CD8+CD57+lymphocytes but not CD57- lymphocytes spontaneously release a solube inhibitor of cytolytic functions (ICF). This inhibitory activity of alveolar CD8+CD57+ cells is mediated by a glycosylated protein which is distinct from tumor necrosis factor-alpha (TNF alpha), TNF beta, transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, interferon alpha (IFN alpha), interferon gamma (IFN gamma), and prostaglandins. The release of such an inhibitor of killer cell functions by CD8+CD57+ lymphocytes in the lungs, which are an important interface between the sterile body and the antigen-laden environment, may play a role in the local control of cell immunity.

AIDS-Related Opportunistic Infections↗
PubMed1994

Late CD8+ lymphocytic alveolitis after allogeneic bone marrow transplantation and chronic graft-versus-host disease.

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.

Adult↗
PubMed1994

T lymphocyte subsets in primary antiphospholipid syndrome.

OBJECTIVE: To study T, natural killer (NK) and B blood cell subsets in primary antiphospholipid syndrome (APS). METHODS: We studied 10 patients with primary APS and 12 healthy subjects. Blood lymphocytes counts, proportions of B cells (CD19+), total CD5 and CD5 B cells, NK cells (CD16+CD56+), T cells (CD3+), CD4+ helper (naive CD4+CD45RA+, memory CD4+CD45RO+ and CD4+CD29+, activated CD4+CD25+), CD8 (immunoregulatory CD8+CD57+, activated CD8+HLA-DR+) T cell subsets were measured by flow cytometry analysis. RESULTS: In the primary APS group, we observed a lower total lymphocyte count (p = 0.009), an expansion of naive CD4 cells (p = 0.025), a lower proportion of memory CD4 cells (p = 0.04) and an increased ratio of naive/memory CD4 cells (p = 0.015). CONCLUSION: Blood T cells phenotypes in primary APS differ markedly from healthy controls, indicating that immunologic abnormalities in primary APS might extend beyond autoantibody production.

Adult↗
PubMed1994

SCID-Hu mouse as a model for human lung HIV-1 infection.

HIV induces a multi-organ infection with a dual tropism for both lymphocytes and monocytes/macrophages. The lung is a target both for HIV infection and HIV-related opportunistic infections. The SCID mouse has provided the opportunity to develop a small animal model for HIV infection. However, HIV-1 infection of the human fetal thymus and liver (SCID Liv/Thy) implanted in these mice occurred only after direct intraimplant injection of HIV-1 and the resultant HIV-1 infection was restricted to the human thymus. Here we report that human foetal lung can develop in SCID Liv/Thy mice resulting in the development of normal human alveolar and bronchiolar lung compartments which can be productively infected with cell-free HIV-1 virus, leading to a systemic and bifocal infection. This SCID-Hu model should be useful for studying AIDS physiopathology, human viruses with lung tropism and for helping to define gene therapy protocols in lung human cells in vivo.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A novel mode of human immunodeficiency virus type 1 (HIV-1) activation: ligation of CD28 alone induces HIV-1 replication in naturally infected lymphocytes.

Induction of human immunodeficiency virus (HIV) replication in infected CD4+ T lymphocytes requires cellular activation. The ligation of CD28, a signal-transducing receptor with a natural ligand on activated B cells and antigen-presenting cells, provides a costimulating signal for interleukin 2 production and T-cell proliferation as well as coactivation of the transfected HIV long terminal repeat in Jurkat cells. The aim of the present study was to investigate the ability of CD28 ligation to activate HIV type 1 (HIV-1) replication in naturally infected CD4+ lymphocytes either alone or in combination with immobilized anti-CD3 monoclonal antibody. Our results show that HIV-1 was successfully isolated from 16 of 28 patients. For 5 of these 16, virus was isolated only when anti-CD28 was added in combination with the anti-CD3. Moreover, stimulation by anti-CD28 alone induced HIV-1 replication in 5 of 12 patients tested, in the absence of cell proliferation. We found no correlation between the level of CD3- or CD28-induced proliferative response and induction of HIV-1 replication. Therefore, CD28 ligation, a nonmitogenic CD4+ T-cell activation signal, is sufficient to induce transcription and replication of HIV-1 in naturally infected lymphocytes.

Antigens, CD↗
PubMed1992

[Amplification of a circulating CD4+CD7- T lymphocytes subset in kidney transplantation].

A minor subset of CD4+ T-cells (10 +/- 4 percent) that does not express the CD7 antigen is detectable in normal individuals. These CD4+CD7- T-cells have lower proliferative capacities than autologous CD4+CD7- T-cells. We observed an expansion of CD4+CD7- peripheral T-cells in 45 kidney transplant recipients. The CD4+CD7- TL expansion (23 +/- 20 percent was observed in both short term (< 6 months, n = 20) and long term transplanted patients (> 3 years, n = 25). These results significantly differed from those observed in patients on dialysis (10 +/- 4 percent, P < 0.002). The percentages of CD4+CD7- TL in kidney recipients are significantly correlated with the percentages of CD4+CD57+ and CD8+CD57+ T-cells subsets. A three-color immunofluorescence analysis indicated that 75 percent of the CD4+CD7- TL express the CD57 molecule contrasting with those in normal individuals (0.3 percent). Purified CD4+CD7- T-cells from kidney recipients have lower proliferative responses after PHA, CD2 and CD3 stimulations than autologous CD4+CD7+ TL. The proliferative response is partially restored by the addition of anti-CD28 moAb or IL2. We have highlighted, in kidney recipients with good graft function, an expansion of CD4+CD7- T lymphocytes which could be associated with CD4+ T-cell anergy and tolerance.

Antigens, CD↗
PubMed1992

Consistency of routine measurements of CD4+, CD8+ peripheral blood lymphocytes.

In order to evaluate the reliability of CD4 and CD8 T lymphocyte counts in large scale studies, a quality control study was performed in 12 French laboratories. CD4 and CD8 counts, assessed by various haematological and immunological techniques, were compared in order to assess possible differences between the laboratories and the techniques used. Our data showed that (a) the consistency of CD4 measurements was satisfactory since the between-laboratory coefficient of variation for absolute CD4 cell numbers above 200/mm3 was around 15% instead of 5-10% for all laboratories but one; (b) the major sources of variability arose from the use of automatic devices in the two-step measurement procedure: immunophenotyping and haematological counting. These data suggest that multicentre assays of CD4 and CD8 counts result in some increase in their variability. Nevertheless the results of large multicentric trials can be extrapolated with confidence in the routine care of HIV+ patients. Together, the results justified the involvement of several experienced laboratories in a clinical trial of HIV-related disease.

CD4 Antigens↗
PubMed1992

Minocycline-induced cell-mediated hypersensitivity pneumonitis.

OBJECTIVE: To identify the cause of a hypersensitivity pneumonitis and to determine its pathogenesis. DESIGN: Case study. SETTING: Intensive care unit of a referral hospital. PATIENT: A 51-year-old man with chronic bronchitis who developed a hypersensitivity pneumonitis within 1 month after exposure to minocycline, amoxicillin, and erythromycin. INTERVENTION: Sequential bronchoalveolar lavages after reexposure to minocycline and amoxicillin. MEASUREMENTS: Immunologic analysis of the phenotype and function of alveolar lymphocytes. RESULTS: 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. CONCLUSION: These results support the hypothesis of a central role of T lymphocytes in the pathogenesis of drug-related hypersensitivity pneumonitis.

Alveolitis, Extrinsic Allergic↗
PubMed1992

CD8 lymphocytosis and pseudotumoral splenomegaly in HIV infection.

Three patients infected with human immunodeficiency virus (HIV) presented with pseudotumoral splenomegaly, CD8 lymphocytosis (3.5-5.1 x 10(9)/l), and hypergammaglobulinaemia. Spleen and bone marrow showed diffuse CD8 lymphocyte and plasma-cell infiltration. Amplification of the T-cell-receptor gamma chain gene did not reveal any clonal T-cell population. Phenotypic analysis showed a predominance of CD8/CD57 suppressor T cells with expression of activation markers (DR and CD38). No cytotoxic T lymphocytes specific for HIV could be detected. The three patients shared the HLA haplotype A1, B8, DR3. The association with this haplotype suggests a genetically determined host immune response to HIV.

Acquired Immunodeficiency Syndrome↗