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Biomedical subjects

R S Wallis

Publications and source records attributed to R S Wallis.

At least 19 recordsLinked to original sources
PubMed1992

Macrophages, mycobacteria and HIV: the role of cytokines in determining mycobacterial virulence and regulating viral replication.

The marriage of two scourges, one old (mycobacterial disease) and one new (HIV), has presented an enormous challenge to the medical and public health communities, and has stirred renewed interest in mechanisms for immune control of mycobacterial infection. Virulence of both M. avium and M. tuberculosis appears to be inversely related to the capacity of the microorganisms to induce production of protective cytokines in infected hosts. TNF alpha and IFN gamma are central to this process, and mycobacterial polysaccharides may be their main determinant. Despite these similarities, M. tuberculosis and M. avium cause illnesses at the polar extremes of HIV disease. Tuberculosis, occurring early in the course of HIV disease, may promote HIV replication in otherwise latently infected cells via induction of cytokines. As such, the potential exists for accelerated progression to AIDS due to the mutual synergy of these pathogens.

AIDS-Related Opportunistic Infections↗
PubMed1992

Duration of fever during treatment of infective endocarditis.

We reviewed the duration of fever among 123 patients treated for infective endocarditis at University Hospitals of Cleveland between 1972 and 1984. One half of these patients became afebrile within 3 days after initiation of antibiotic therapy and nearly three quarters were afebrile after 1 week of therapy. After 2 weeks of therapy, nearly 90% had defervesced. Endocarditis due to Staphylococcus aureus or gram-negative bacilli, and culture-negative endocarditis, were associated with prolonged fever. Microvascular phenomena, major vessel embolization, or vegetations seen on 2-D echocardiogram also were associated with prolonged fever. Multivariate analysis revealed that only microvascular phenomena or major vessel embolization were independently associated with longer duration of fever. Endocarditis-associated mortality among patients who remained febrile after 1 week of therapy was 18%, and this was greater than the 2% mortality among patients who defervesced (p less than 0.002). These data suggest that prolonged fever during treatment of infective endocarditis is often due to tissue infarction or vascular injury. Prolonged fever also identifies patients at higher risk of a fatal outcome.

Age Factors↗
PubMed1991

T cell activation by mycobacterial antigens in inflammatory synovitis.

To define which mycobacterial antigens were responsible for the activation of synovial fluid T lymphocytes, acetone-precipitated Mycobacterium tuberculosis (AP-MT) antigens were separated into five fractions following polyacrylamide gel electrophoresis and added to the mononuclear cell cultures of patients with inflammatory synovitis. Fractions 2 (50 to 70 kDa) and 5 (less than 28 kDa) resulted in significantly more proliferation than that of fractions 1, 3, and 4. The response to a purified mycobacterial 65-kDa heat shock protein (hsp), which migrated in fraction 2, was highly correlated (r = 0.89, P less than 0.001) with the response to the crude AP-MT. The proliferative response to a different hsp. the Escherichia coli DnaK, by synovial fluid lymphocytes was marginal. Analysis of the synovial fluid T cell response to mycobacterial culture filtrates by T cell Western blotting revealed dominant responses to antigen(s) in the range of 31 to 21 kDa in each responding patient, although no other consistent pattern of T cell activation was noted. Three lines of evidence suggested that the response to the low molecular weight fractions was directed against degradation fragments of the 65-kDa protein. These observations suggest that the activation of T lymphocytes obtained from inflammatory synovial fluids by crude mycobacterial antigens was due in large part to recognition of the 65-kDa mycobacterial hsp.

Antigens, Bacterial↗
PubMed1991

Human immune response to Mycobacterium tuberculosis antigens.

Little is known about the immunodominant or protective antigens of Mycobacterium tuberculosis in humans. Cell-mediated immunity is necessary for protection, and healthy tuberculin-positive individuals are relatively resistant to exogenous reinfection. We compared the targets of the cell-mediated immune response in healthy tuberculin-positive individuals to those of tuberculosis patients and tuberculin-negative persons. By using T-cell Western blotting (immunoblotting) of nitrocellulose-bound M. tuberculosis culture filtrate, peaks of T-cell blastogenic activity were identified in the healthy tuberculin reactors at 30, 37, 44, 57, 64, 71 and 88 kDa. Three of these fractions (30, 64, and 71 kDa) coincided with previously characterized proteins: antigen 6/alpha antigen, HSP60, and HSP70, respectively. The blastogenic responses to purified M. tuberculosis antigen 6/alpha antigen and BCG HSP60 were assessed. When cultured with purified antigen 6/alpha antigen, lymphocytes of healthy tuberculin reactors demonstrated greater [3H]thymidine incorporation than either healthy tuberculin-negative controls or tuberculous patients (8,113 +/- 1,939 delta cpm versus 645 +/- 425 delta cpm and 1,019 +/- 710 delta cpm, respectively; P less than 0.01). Healthy reactors also responded to HSP60, although to a lesser degree than antigen 6/alpha antigen (4,276 +/- 1,095 delta cpm; P less than 0.05). Partially purified HSP70 bound to nitrocellulose paper elicited a significant lymphocyte blastogenic response in two of six of the tuberculous patients but in none of the eight healthy tuberculin reactors. Lymphocytes of none of five tuberculin-negative controls responded to recombinant antigens at 14 or 19 kDa or to HSP70. Antibody reactivity generally was inversely correlated with blastogenic response: tuberculous sera had high titer antibody to M. tuberculosis culture filtrate in a range from 35 to 180 kDa. This is the first systematic evaluation of the human response to a panel of native and recombinant antigens in healthy tuberculin reactors and tuberculous patients. Antigens which stimulated prominent lymphocyte blastogenic responses were identified in seven fractions on T-cell Western blot analysis. Two of these may represent previously characterized proteins; the others may contain immunodominant proteins that will require further characterization.

Antibodies, Bacterial↗
PubMed1991

Human Mycobacterium tuberculosis-reactive CD4+ T-cell clones: heterogeneity in antigen recognition, cytokine production, and cytotoxicity for mononuclear phagocytes.

CD4+ T cells regulate the protective immune response which follows exposure to Mycobacterium tuberculosis by activating macrophages through the cytokines the CD4+ T cells secrete. In addition CD4+ T cells have been shown to be directly cytotoxic for antigen-pulsed mononuclear phagocytes (monocytes-macrophages). To explore the functional interaction between mycobacterial antigen-specific CD4+ T cells and mononuclear phagocytes further, CD4+ T-cell clones were derived from healthy purified protein derivative-positive individuals. Five T-cell clones were selected for detailed analysis. None responded to the purified recombinant or native mycobacterial antigens of 14, 19, 65, 71, and 30 (alpha-antigen/Ag6) kDa. However, the T-cell clones demonstrated heterogeneity in antigen recognition as measured by their Western blot (immunoblot) responses. Some T-cell clones made only interleukin 2, while others made only interleukin 4; all produced gamma interferon, although in differing amounts. Four of five T-cells clones were cytotoxic for purified protein derivative-pulsed monocytes at 1:1 and 10:1 effector-target cell ratios. When monocytes infected with live M. tuberculosis were used as targets, comparable levels of cytotoxicity were observed. The cytotoxicity was major histocompatibility complex class II restricted and inhibited by antibodies to ICAM-1 and LFA-1 and not by antibodies to tumor necrosis factor alpha, lymphotoxin, and gamma interferon. Cytotoxicity by CD4+ T cells for monocytes pulsed with mycobacterial antigens or infected with live M. tuberculosis is a common property of these cells and appears to be independent of the repertoire of lymphokines produced and not limited to recognition of defined mycobacterial heat shock proteins. Lysis of heavily infected mononuclear phagocytes may be one manner in which CD4+ T cells regulate host immune response to M. tuberculosis.

Antigens, Bacterial↗
PubMed1991

Direct mitogenic properties of interleukin-1.

Optimal lymphocyte activation generally requires two concurrent signals, one involving the T cell receptor, and another supplied by an accessory cytokine such as interleukin-1. We investigated the conditions under which partial cellular activation occurs in the absence of signal to the T cell receptor. Both murine thymocytes and the T cell clone D10.G4.1 responded to recombinant interleukin-1 in the absence of a mitogenic signal, although the magnitude of these responses was smaller and required higher concentrations of interleukin-1 than if a comitogen had been present. Interleukin-1 and interleukin-6 in combination were synergistic and induced tritiated thymidine incorporation in D10.G4.1 cells equal to 15% of that obtained with optimal concentrations of concanavalin A. Such synergy suggests that a significant degree of nonspecific activation of lymphocytes may occur in the presence of combinations of monocyte-derived cytokines.

Animals↗
PubMed1990

Induction of interleukin 1 and tumor necrosis factor by mycobacterial proteins: the monocyte western blot.

Infection with Mycobacterium tuberculosis involves mononuclear phagocytic cells as hosts to intracellular parasites, accessory cells in the induction of the immune response, effector cells for mycobacterial killing, and targets of cytotoxic lymphocytes. When stimulated by whole mycobacteria or various mycobacterial preparations, monocytes and macrophages produce the cytokines interleukin 1 and tumor necrosis factor, which possess multiple functions, including immune induction, and may be responsible for the fever and cachexia prominent in tuberculosis. To identify mycobacterial proteins that may directly activate production of these cytokines, culture filtrate of M. tuberculosis that had been subjected to gel electrophoresis and transferred to nitrocellulose paper was used to stimulate monocyte production of cytokines. Fractions representing molecular weights of 46,000 and 20,000 consistently induced both interleukin 1 and tumor necrosis factor. The magnitude of the monocyte responses to these fractions was similar to that to intact mycobacteria or optimal concentrations of lipopolysaccharide. This stimulatory effect was not due to contamination with either bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as it was abolished by digestion with Streptomyces griseus protease but was unaffected by ammonium sulfate precipitation, preincubation with polymyxin B, or depletion of lipoarabinomannan by immunoaffinity chromatography. Proteins identified by this system may have considerable potential as immunogens, as the capacity to directly stimulate mononuclear phagocyte production of cytokines is an essential property of adjuvants.

Animals↗
PubMed1990

Cell membrane is a major locus for ultraviolet B-induced alterations in accessory cells.

In vitro ultraviolet B (UVB) irradiation of human blood monocytes inhibits their accessory cell function for antigen- and mitogen-induced T cell responses. These studies were designed to characterize the nature of the UVB-induced defect in human monocyte accessory cell function. Irradiated monocytes were deficient in their ability to serve as accessory cells for OKT3-induced T cell activation. In vitro exposure of monocytes to 100 J/m2 UVB completely inhibited the T cell proliferative response (51502 cpm, non-UVB-irradiated; 302 cpm, UVB-irradiated). Analysis of the accessory signals altered by UVB indicated that irradiated monocytes were incapable of binding to OKT3 molecules attached to the CD3 antigen on T cells. Provision of an alternative mechanism for binding of OKT3 molecules by attaching anti-mouse IgG to the bottom of microtiter wells completely restored accessory cell function. Further characterization of the defect demonstrated that UVB radiation did not deplete p72 Fc receptors from the surface of irradiated monocytes. However, UVB exposure did produce a dose-dependent decrease in monocyte membrane expression of ICAM-1. It is proposed that UVB radiation leads to changes within the cell membrane that inhibit the ability of monocytes to express selected molecules necessary for binding of T cells.

Antibodies, Monoclonal↗
PubMed1989

Dyscoordinate expression of tumor necrosis factor-alpha by human blood monocytes and alveolar macrophages.

Previous studies have shown that human alveolar macrophages produce less interleukin-1 (IL-1) in response to lipopolysaccharide (LPS) than do their precursors, blood monocytes. The purpose of this study was to compare the capacities of alveolar macrophages and blood monocytes to synthesize tumor necrosis factor (TNF) in response to LPS. Alveolar macrophages were obtained by bronchoalveolar lavage of healthy nonsmoking subjects, and blood monocytes were obtained by adherence of mononuclear cells to plastic. TNF activity was measured in supernatants and cell lysates as cytotoxicity to L929 fibroblasts (uptake of neutral red at 570 nm). TNF activity of alveolar macrophages stimulated at 10(6) cells/ml with LPS (10 micrograms/ml) for 16 h was 596 +/- 367, and of blood monocytes it was 60 +/- 84 U/ml (mean +/- SD, p less than 0.005). At no concentration of LPS and at no period of stimulation did alveolar macrophages express less TNF activity than did blood monocytes. In concurrent experiments, supernatants of LPS-stimulated alveolar macrophages contained less IL-1 activity than did blood monocytes. Lysates of both cell types contained less than 20% of total TNF activity. The TNF activity of LPS-stimulated alveolar macrophages was neutralized greater than 99% by monoclonal antibody to TNF-alpha; control monoclonal antibody OKT3 had no effect. Next, alveolar macrophages and blood monocytes were biosynthetically labeled with [3H]leucine during incubation with LPS; supernatants were immunoprecipitated with anti-TNF, and precipitates were electrophoresed on polyacrylamide gels. Autoradiographs indicated that immunoreactive TNF was produced by both blood monocytes and alveolar macrophages and that the relative molecular weights were identical (17,000).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Identification of antigens of Mycobacterium tuberculosis using human monoclonal antibodies.

Pleural tuberculosis constitutes a human model of local protective immunity to mycobacterial infection as the disease is usually self-limited and recurrent pleurisy is rare. To identify potentially protective antigens of Mycobacterium tuberculosis, 37 human pleural fluid B cell clones were established using EBV and their supernatants assayed by ELISA and Western blot for antibody reactivity with M. tuberculosis sonicate and culture filtrate. One antibody identified 29,000, 31,000, and 33,000 bands in culture filtrate, and 31,000, 33,000, and 47,000 bands in sonicate; its species reactivity by ELISA was limited to M. tuberculosis. Eight antibodies identified a 31,000 band in culture filtrate and a 68,000 band in M. tuberculosis sonicate, suggesting recognition of a secreted antigen. The species crossreactivity of these eight antibodies extended to M. avium. Six antibodies identified multiple bands and had crossreactivity that included M. avium and M. kansasii. There was no reactivity with recombinant M. tuberculosis 65,000 antigen. Tuberculous pleurisy may prove useful in the identification of potentially protective mycobacterial antigens, particularly those secreted during active infection, and thus accessible to the human immune response.

Antibodies, Monoclonal↗
PubMed1988

Expression of tumor necrosis factor in vitro by human mononuclear phagocytes stimulated with whole Mycobacterium bovis BCG and mycobacterial antigens.

Four mycobacterial preparations directly stimulated human blood monocytes and alveolar macrophages to produce tumor necrosis factor (TNF). Monoclonal antibody against TNF blocked (99%) TNF activity. Lipopolysaccharide was not responsible for the TNF activity generated; activity was unaffected in the presence of polymyxin B.

Antigens, Bacterial↗
PubMed1988

The immunology of tuberculous pleurisy.

Tuberculous pleurisy results when a subpleural nodule discharges mycobacterial antigens into the pleural space of a hypersensitive host. The clinical syndrome is a reflection of an in situ delayed-type hypersensitivity reaction in which plasma proteins are exuded into the pleural space and T-helper cells accumulate, proliferate, and produce, and release inflammatory mediators. The immune response initially contains the local infection, but in the absence of therapy, the host is at great risk of developing tuberculosis during the next 5 years. The focal accumulation of vigorously responsive T-helper cells and activated B cells in the pleural space may prove useful in identifying mycobacterial constituents which are immunogenic and possibly candidate vaccine antigens.

Animals↗
PubMed1988

Tumor necrosis factor is the major monocyte product that increases complement receptor expression on mature human neutrophils.

Interleukin-1 (IL-1) and other monocyte products have several important effects on the systemic response to infection in addition to their roles in lymphocyte stimulation. The present studies were carried out to determine whether products of stimulated monocytes activated circulating neutrophils (PMN) to increase expression of receptors for C3b (CR1) and C3bi (CR3), which are necessary for optimal margination, migration, and phagocytosis. Supernatants of human mononuclear cells that had been stimulated with lipopolysaccharide (LPS) or purified protein derivative (PPD) contained both tumor necrosis factor (TNF) and IL-1 and increased CR1 and CR3 expression on isolated PMNs. Supernatants of unstimulated cultures, media alone, or LPS or PPD alone had little or no effect. Supernatant effects were detectable at 1:3,000 final dilution and appeared to have a characteristic slow time course. These supernatants also caused dose- and time-dependent secretion of PMN granular constituents, but maximal receptor expression was accompanied by secretion of less than 10% of the cells' content of lysozyme and less than 16% of the B12 binding protein. Immunoadsorption studies showed that the supernatant's activity could be removed by anti-TNF but not by anti-IL-1. Recombinant IL-1 had no effect on receptor expression, but recombinant TNF increased CR1 and CR3 expression with kinetics similar to the supernatants. These results thus indicate that TNF is the major monocyte product that increases CR1 and CR3 expression on mature blood neutrophils. This would result in increased margination and phagocytic activity and may be an important systemic effect that would help the host eradicate infection.

Calcium↗
PubMed1987

Deleterious effect of ultraviolet-B radiation on accessory function of human blood adherent mononuclear cells.

The effects of ultraviolet-B radiation (UV-B) on accessory function of human blood adherent mononuclear cells (ADH) for antigen and mitogen-induced responses, and production by ADH of the amplifying cytokine interleukin 1 (IL-1) were examined. Responder lymphocytes were rendered accessory cell dependent by treatment of nonadherent cells with OKIal+complement. UV-B depressed accessory function of ADH in a dose-dependent manner. UV-B at 5 mJ/cm2 decreased accessory function of 2 x 10(4) ADH for tetanus toxoid-induced responses (measured as incorporation of 3H-thymidine) by 84% (P less than 0.001, n = 6) and phytohaemagglutinin-induced responses 91% (P less than 0.001, n = 4). UV-B also decreased accessory activity of peripheral blood mononuclear cells but not Epstein-Barr virus-transformed B cells for a PPD-reactive T cell line. Viability was approximately 90% 0-72 h after exposure of ADH to 5 mJ/cm2 of UV-B. Interleukin 1 (IL-1) activity of supernatants of ADH was assayed on C3H/HeJ mouse thymocytes. Pretreatment of ADH with 5 mJ/cm2 UV-B decreased lipopolysaccharide-stimulated IL-1 activity from 169 +/- 34 (mean U/ml +/- s.e.) to 4 +/- 1 (P less than 0.01, n = 4). Lysates of UV-B irradiated. LPS-stimulated ADH had no discernible IL-1 activity. Addition of IL-1 partially restored accessory activity of UV-B irradiated ADH for lymphocyte responses to TT. Exposure of ADH to TT or PHA for 30 min before irradiation blocked the inhibitory effect of UV-B on accessory activity. Thus, low doses of UV-B are deleterious to accessory function and to production of IL-1 by ADH. Interference with production of cytokines and with initial interactions of accessory cells with antigen and mitogen may be critical to the effects of UV-B on immunoregulatory function of ADH.

Antigen-Presenting Cells↗
PubMed1986

Increased interleukin-1 production and monocyte suppressor cell activity associated with human tuberculosis.

Interleukin-1 (IL-1) production by blood monocytes and blastogenesis produced by tuberculin purified protein derivative (PPD) in blood T lymphocytes were examined in patients with pulmonary tuberculosis. Monocytes were isolated from blood mononuclear cells by plastic adherence, and IL-1 activity was determined in the mouse thymocyte proliferation assay. Monocytes from patients with tuberculosis produced significantly higher activities of IL-1 than did those from healthy tuberculin reactors when stimulated with lipopolysaccharide (LPS) (patients, 56.1 +/- 20.0 U/ml; healthy control subjects, 7.3 +/- 1.7 U/ml; p less than 0.05) or PPD (patients, 28.1 +/- 7.2 U/ml; healthy control subjects, 9.5 +/- 2.9 U/ml; p less than 0.05). In contrast, PPD-induced blastogenic responses in peripheral blood mononuclear cells (PBMC) from the patients were lower than those from healthy subjects (patients, 4,506 +/- 1,145 cpm; healthy control subjects, 14,655 +/- 2,240 cpm; p less than 0.005), and IL-1 production by monocytes showed a positive correlation with monocyte suppressor activity for PPD-induced blastogenesis. Moreover, exogenous IL-1 was capable of suppressing antigen-induced blastogenesis of PBMC from healthy subjects. These data suggest that monocytes from patients with pulmonary tuberculosis are activated to produce or secrete increased levels of IL-1 and that IL-1 may be a mediator of suppressor cell function.

Adult↗