T cell deletion and unresponsiveness induced by intrathymic injection of staphylococcal enterotoxin B.

Intrathymic injection of alloantigens appears to be the most efficient route to induce alterations of T cell reactivity. In the present study, we explored the modifications of Vbeta8.1, 8.

Expression and modulation of ICAM-1, TNF-alpha and RANTES in human alveolar macrophages from lung-transplant recipients in vitro.

Alveolar macrophages (AMs) play a central role in pulmonary inflammation in response to local stimuli. As a model for investigating anti-inflammatory drugs, we studied the effects of the cyclohexadepsipeptide antibiotic, fusafungine, and that of the glucocorticoid dexamethasone on the expression of ICAM-1, TNF-alpha and RANTES, induced in vitro by rIFN-gamma in human AMs freshly isolated from bronchoalveolar lavage fluid (BAL) obtained in lung-transplanted patients. ICAM-1 antigen expression, induced on AMs after 24 h of culture, was significantly inhibited by fusafungine in a concentration-dependent manner, as measured by flow cytometry analysis using an anti-CD54 monoclonal antibody.

Expression of ICAM-1 and TNF alpha in human alveolar macrophages from lung-transplant recipients.

Local activation of macrophages may play an important role in the immune process of pulmonary infections and in the inflammatory response of lung allograft rejection. To document macrophage activation within human lung allografts displaying various complications, we have investigated ICAM-1 expression in freshly isolated alveolar macrophages (AM) from lung-transplant recipients by immunocytofluorimetric analysis, and rIFN gamma induced in vitro by ELISA. A total of 21 bronchoalveolar lavage fluids (BAL) from 13 transplanted patients displaying no complication, acute rejection, bacterial/fungal infection, or CMV infection entered the study.

Modulation of ICAM-1 expression in human alveolar macrophages in vitro.

Modulation of intercellular adhesion molecule-1 (ICAM-1) expression may be a basic mechanism by which alveolar macrophages (AMs) regulate the inflammatory process in the lung in response to local stimuli. As a model for studying the anti-inflammatory activity of drugs on human AMs, we investigated the effects of fusafungine, an antibiotic for local use by aerosol with anti-inflammatory properties, and that of the glucocorticoid dexamethasone, on ICAM-1 expression induced in vitro by recombinant interferon-gamma (rIFN-gamma). ICAM-1 protein expression was studied on AMs by means of flow cytometry with an anti-CD54 monoclonal antibody; messenger ribonucleic acid (mRNA) levels were determined by reverse transcriptase-polymerase chain reaction (RT-PCR).

[Expression of intercellular adhesion molecule 1 (ICAM-1) on human alveolar macrophages].

Modulation of intercellular adhesion molecule 1 (ICAM-1) expression on alveolar macrophages (AM) may be one of the the basic mechanisms by which AM regulate the course of inflammatory response during pulmonary allograft rejection and infectious processes by mediating macrophage-lymphocyte interactions. As a model for studying anti-inflammatory activity of drugs on AM, we have investigated the effect of fusafungine, a local antibiotic which displays also anti-inflammatory properties, on the regulation of ICAM-1 membrane expression induced in vitro by stimulating AM from lung-transplant recipients. We have studied ICAM-1 membrane expression by immunocytofluorometric analysis using the anti-CD54 monoclonal antibody.

Particular phenotypic profile of blood lymphocytes during obliterative bronchiolitis syndrome following lung transplantation.

Bronchiolitis obliterans syndrome (OBS) remains the major complication in long-term survivors with heart-lung transplants, occurring in up to 50% of patients who survived the first year postsurgery. Until now, a significant decrease in small airway flow parameters has represented the most sensitive index for the detection of early OBS. Using immunocytofluorometric analysis, in a prospective study we have analysed the phenotype of peripheral blood lymphocyte effector and regulatory subsets in seven patients with inactive well-established OBS as compared with lung transplant recipients without any complication.

Emergence of inflammatory alveolar macrophages during rejection or infection after lung transplantation.

Local activation of macrophages may play an important role in immune complications following lung transplantation. To document such a phenomenon, we have investigated the possible changes of alveolar macrophage surface antigen expression after lung transplantation. Using immunocytofluorometry, we have analyzed the phenotype of alveolar macrophages from 41 bronchoalveolar lavage fluids obtained from 19 lung transplant recipients displaying various complications.

[Humoral and cellular immunologic reactions in various forms of chronic psychiatric diseases].

Studies on the status of the immune system in mental disorders have mostly provided contradictory results. For example, some authors have reported dramatic increases of immunoglobulin G in schizophrenic patients, and others a decrease of immunoglobulin G in the same patients. This prompted us to undertake a study on a large cohort of psychiatric patients (120 schizophrenics, 30 manic-depressives, 8 epileptics, 48 cases of Alzheimer and vascular dementia, 23 cases of alcoholic dementia, 14 cases of childhood psychosis, 47 encephalopaths, and 21 chronic alcoholics), all chronically hospitalized.

[Phenotype profile of blood lymphocytes in bronchiolitis obliterans after lung transplantation].

Bronchiolitis obliterans (BO) remains the major complication in long-term survivors with lung transplants, occurring in up to 30% of them. As a non-invasive follow-up of lung recipients, we studied the phenotype of peripheral blood lymphocyte subsets. Using a flow cytometric analysis, we could define a specific pattern during BO.

Induction of various cytokines in mice and activation of the complement system in rats as a part of the mechanism of action of the Corynebacterium granulosum-derived P40 immunomodulator.

The capacity of the Corynebacterium granulosum-derived P40 immunomodulator to induce in mice the formation of various cytokines IFN, IL-1, IL-2, alpha-TNF as well as to activate the complement system in rats was investigated. The results showed that P40 injected by the intravenous route was capable of inducing the formation of all four cytokines. High levels of IFN were measured 2 h after P40 stimulation and were still present at 24 h.

[Immunocompetence in the elderly].

Ageing is associated with a progressive decline of the immune systems, characterized by impaired T cells and changes in the antigenic repertory related to both the humoral and cell-mediated immune responses. The major alterations have been demonstrated in the T cells which undergo functional changes, such as a decrease in precursor frequencies of helper and cytotoxic T-cells, and accumulation of T cells which does not respond to activators. In general, T cell-dependent, cell-mediated responses decline with age.

Standardized mouse infection models as a way of evaluating the potency of anti-infectious agents.

Standardized bacterial and viral mouse infection models have been developed. Infections with extracellular bacteria (K. pneumoniae, S.

Assessment of the anti-viral effect of a short-term oral treatment of mice with live Saccharomyces cerevisiae cells.

For assessing the efficacy of antiviral treatments, influenza and herpes virus HSV-1 infections of varying degrees of severity have been produced. The infections proved to be reproducible with respect to both their course and death rate. These infections also exhibited a course slow enough to permit the assessment of treatments under conditions mimicking human infections and lent themselves to the choice of the best adapted strategy to treat an infection.

Anti-infectious effect of C granulosum-derived P40 immunomodulator given by aerosolization and intranasal instillation.

It is known that C granulosum-derived P40 immunomodulator displays strong anti-microbial effects in mice by the intravenous route. Since microbial contamination of humans occurs in many instances via the airways, the effect of P40 on infections was investigated when it was given intranasally or by aerosolization. In order to augment its bioavailability, P40 was derivatized by coupling with polylysine chains (P40-PL).

Pneumococcal vaccination of elderly individuals.

Pneumococcal infections are still a cause of high morbidity and mortality in elderly populations. Since antibiotics are not wholly effective, vaccination should be performed. The response to pneumococcal vaccination of a limited group of elderly persons aged 60 to 90 years was studied.

[The usefulness of vaccination in elderly persons].

The antitetanus, antipneumococcal and antiinfluenza immune status, as well as the efficacy of vaccination have been evaluated in the elderly. Ages of the studied populations ranged from 60 to 98 years. Before vaccination, only half of the tested population was found to be protected against tetanus.

Usefulness of influenza vaccination in the elderly.

Since influenza morbidity and mortality are high in the elderly, the usefulness of vaccination has been evaluated. One hundred and twenty-six older persons aged 60-90 yr were given a vaccine consisting of the 3 antigens Singapore, Shanghaï and Yamagata, the latter 2 being new antigens. Antibody levels for each of the antigens were determined by ELISA calibrated in HA units prior to and 1 month after vaccination.

Monitoring of the response of elderly individuals to pneumococcal vaccination with the aid of a novel ELISA.

An ELISA for assessing pneumococcal anticapsular antibodies in human sera is described. Sensitization was carried out by adding to avidin-coated polystyrene plates biotinylated capsular polyosides. This ELISA was used for the determination of anticapsular antibody levels in pre- and post-immunization sera from 20 elderly individuals.

Use of live Saccharomyces cerevisiae cells as a biological response modifier in experimental infections.

A short-term oral administration of live Saccharomyces cerevisiae cells, strain Sillix Hansen DSM 1883, resulted in enhanced resistance of mice toward infections with K. pneumoniae. S.

A dot-ELISA intended for the specific and simultaneous detection of antibodies directed to antigens derived from Toxoplasma gondii, rubella virus, cytomegalovirus, and type 1 and type 2 herpesviruses.

A procedure for the routine and simultaneous laboratory detection of IgG antibodies produced in humans in the course of various infectious diseases is described. The procedure, based on dot-enzyme-linked immunosorbent assay (ELISA), used single nitrocellulose strips onto which several antigens were dotted in close proximity. Optimal conditions were specified that allowed the unequivocal and simultaneous detection of IgG antibodies specifically directed against Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus type 1 and type 2 antigens.

A dot-ELISA for the detection of IgG antibodies to mumps and varicella viruses.

An enzyme-linked immunosorbent assay using nitrocellulose strips (dot-ELISA) for the routine laboratory detection of IgG antibodies to mumps and varicella viruses is described. The virus antigens are dotted onto nitrocellulose strips, and the dotted strips are incubated with the sera to be tested. The bound antibodies are revealed using enzyme-labeled antihuman IgG antibodies.

[Prevention and therapeutical trials of a few current viral diseases].

Vaccines afford now good prevention of many viral diseases including Hepatitis B. In revenge, attempts of immunization against Herpes Virus types I and II did not result in large scale application of vaccination. Research for a vaccine against HIV encounters many difficulties due to virus variability and host reactions.

Potentiation by nonspecific immunostimulation of the efficacy of antibiotics in the treatment of experimental bacterial infections.

In the present investigation, mouse infection models with either intracellular or extracellular bacteria were designed in order to assess the effect of nonspecific immunostimulation with the C. granulosum-derived P40 immunomodulator on infection treatment, performed with doses of antibiotics achieving a low percentage of cures. The results obtained showed that nonspecific immunostimulation was able to significantly enhance antibiotic therapy efficacy.