Search PubMed⌕ Search

Biomedical subjects

J J Ellner

Publications and source records attributed to J J Ellner.

At least 127 records · Page 7Linked to original sources
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

The influence of human immunodeficiency virus infection on tuberculosis in Kampala, Uganda.

The clinical, radiographic, and microbiologic features of 59 patients with pulmonary tuberculosis in Kampala, Uganda were studied and correlated with the serologic reactivity to the human immunodeficiency virus (HIV) of these patients. Two-thirds of the patients with tuberculosis were HIV-seropositive. Histories of fever and weight loss were more prominent in HIV-seropositive patients, and perihilar and basilar infiltrative diseases were more frequently seen in HIV-seropositive patients. Although all patients responded similarly to drug therapy, cutaneous drug reactions were seen in nearly one-third of HIV-seropositive patients receiving thiacetazone.

Adolescent↗
PubMed1991

Requirement for cell-to-cell contact for the immunosuppressive activity of human alveolar macrophages.

The ability of alveolar macrophages (AM) obtained by bronchoalveolar lavage of healthy volunteers to suppress T lymphocyte responses to the mitogen phytohemagglutinin (PHA) in vitro was investigated. AM but not monocytes (MN) inhibited responses of peripheral blood mononuclear cells (PBMC) to PHA as measured by incorporation of [3H]thymidine [( 3H]TdR) and interleukin-2 (IL-2) expression. Supernatants of AM generated for various periods and with various concentrations of cells did not, however, inhibit PBMC responses to PHA. To examine the role of cell contact in the inhibitory activity of AM, AM or MN were added to PBMC in 6-well plates either directly (in co-culture) or separated by a 0.45-micron filter. MN did not inhibit PBMC blastogenic responses under either condition. AM at a 1:2 ratio with PBMC inhibited blastogenesis by 75 +/- 11% (mean +/- SD, n = 3, P less than 0.01) when cultured directly with PBMC but had no inhibitory effect on blastogenesis when physically separated from target PBMC. AM in co-culture with PBMC also inhibited PHA-stimulated IL-2 production by 70% but did not inhibit IL-2 production when AM were separated from PBMC in dual chambers. To assess the role of the cell surface in the inhibitory activity of AM, AM and MN were fixed with 2% paraformaldehyde. Neither fixed nor unfixed MN inhibited PBMC blastogenic responses, but both fixed and unfixed AM inhibited responses similarly (77 to 95%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Selective expansion of human gamma delta T cells by monocytes infected with live Mycobacterium tuberculosis.

Gamma delta (gamma delta) T cell receptor (TCR) expressing T cells comprise 3% of human peripheral blood lymphocytes, yet their role in the immune response remains largely unknown. There is evidence both in humans and in animal models that these cells participate in the immune response to mycobacterial antigens. In mice, exposure to mycobacterial antigens leads to the expansion of gamma delta T cells in draining lymph nodes and lungs. In humans, gamma delta T cell lines with reactivity to mycobacterial antigens have been derived from synovial fluid of a rheumatoid arthritis patient, skin lesions of leprosy patients, and peripheral blood of a healthy tuberculin reactor. Very little is known, however, about the factors which induce human gamma delta T cells to expand. In studies comparing the human T cell response to live and heat-killed Mycobacterium tuberculosis (MT), we have found that monocytes infected with live MT are very effective inducers of human gamma delta T cell expansion. After 7 d of exposure to live MT, gamma delta T cells were greatly increased in all healthy tuberculin reactors (PPD+) tested and frequently were the predominant T cell population. In contrast, heat-killed MT or purified protein products of MT induced a CD4+, alpha beta TCR+ T cell response with very little increase in gamma delta T cells. Furthermore, a similar selective induction of gamma delta T cells was observed when monocytes infected with live Salmonella were used to stimulate T cells. Heat-killed Salmonella, like heat-killed MT, induced a predominantly CD4+ alpha beta TCR+ T cell response. These findings suggest that human gamma delta T cells are a major reactive T cell population during the early stages of infection with living intracellular bacteria and are therefore likely to exert an important role in the initial interaction between host and parasite.

Antigens, Bacterial↗
PubMed1991

A 19-year follow-up of tuberculin reactors. Assessment of skin test reactivity and in vitro lymphocyte responses.

Tuberculin skin test reactivity decreases with time such that repeat PPD skin testing may result in reactions of less than 10 mm. This reactivity may be boosted in some individuals with a second tuberculin skin test. The immunologic basis of these observations remains unclear. We studied the relationship between skin-test reactivity and in vitro blastogenic response to PPD in a cohort of 22 individuals (aged 28 to 81 years) known to be tuberculin reactors (induration greater than or equal to 10 mm) in 1970. In 1989, 18 subjects remained reactive to PPD on the first skin test and responded to PPD in vitro (mean incorporation of 3H-thymidine by peripheral blood mononuclear cells, 22,650 cpm). Three subjects reverted (induration in response to PPD less than 10 mm) and lost in vitro reactivity to PPD (mean incorporation of 3H-thymidine, 2,205 cpm). One subject boosted (increase of induration of at least 6 mm to greater than or equal to 15 mm) on the second skin test and showed a concomitant in vitro boost in the blastogenic response to PPD (from 1,008 cpm to 47,837 cpm). In this cohort, interpretation of the two-step tuberculin skin test correlated closely with in vitro proliferative responses. Over a 19-year period, the majority of individuals maintained skin test reactivity and strong in vitro responses to PPD despite a lack of ongoing exogenous exposure to Mycobacterium tuberculosis. The immunologic basis for reversion appears to depend in part on a loss of lymphocyte blastogenic capacity. In the one individual who exhibited the booster phenomenon, repeat antigen stimulation resulted in a dramatic increase in the in vitro blastogenic responses.

Adult↗
PubMed1991

Release of a suppressor cell-inducing factor by monocytes from patients with pulmonary tuberculosis.

We observed that blood monocytes from tuberculous patients secreted a factor which induced suppressor cells. Monocyte-enriched adherent cells were prepared from peripheral blood mononuclear cells (PBMC) of 14 patients with active pulmonary tuberculosis or nine healthy tuberculin skin reactors and were cultured without any stimulus for 5 days. For induction of suppressor cells, PBMC from a healthy tuberculin reactor were cultured with the monocyte culture supernatants (MN SUP). After 2 days, those cells were washed and irradiated, then tested for their ability to suppress blastogenesis in autologous PBMC stimulated with purified protein derivative (PPD). Mean activity of suppressor cell induction in MN SUP of patients with pulmonary tuberculosis was significantly greater than that of healthy controls. In contrast, PPD-induced blastogenic responses in PBMC from tuberculous patients were lower than in controls. When we divided those tuberculous patients into high and low secretor groups on the basis of the magnitude of suppressor cell induction by MN SUP, PBMC from the high secretors had lower direct blastogenic responses to PPD than those of the low secretors. The blastogenic responses of PBMC from the high secretors, but not the low secretors, were significantly lower than those of healthy subjects. MN SUP which contained high suppressor cell-inducing activity had no effect on PPD-induced blastogenesis of PBMC from a healthy donor. These data suggest that monocytes from some tuberculous patients indirectly depress lymphocyte blastogenesis through a suppressor cell-inducing factor.

Adult↗
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

Regulation of antigen-induced blastogenesis and interleukin-2 expression by adherent mononuclear cells in humans infected with Schistosoma mansoni.

The immune response and its regulation by adherent mononuclear cells were investigated in 39 Egyptians aged 13-30 (mean +/- SD, 16.2 +/- 3.6) with chronic Schistosoma mansoni infection (fecal egg excretion, 40-2480 eggs/g; mean, 709 +/- 612). Blastogenesis and production of interleukin-2 (IL-2) by peripheral blood mononuclear cells showed a significant correlation when streptolysin O but not when soluble worm antigenic preparation (SWAP) was used as stimulus. This suggested independent regulation of these responses to SWAP. Thirteen subjects showed SWAP-restricted suppression of blastogenesis but not IL-2 production by adherent cells. Compared with 24 other S. mansoni-infected subjects, they had depressed blastogenic responses to SWAP but comparable SWAP-induced IL-2 production and responsiveness to exogenous IL-2. This study indicates that IL-2 production is not the site of action of parasite antigen-restricted suppressor adherent cells in chronic S. mansoni infection.

Adolescent↗
PubMed1990

Absence of bacteremia with Mycobacterium avium-intracellulare in Ugandan patients with AIDS.

Disseminated infection with Mycobacterium avium-intracellulare is the most common systemic bacterial infection in American patients with the acquired immunodeficiency syndrome. Blood cultures for mycobacteria were obtained from 50 severely ill Ugandan patients fulfilling the World Health Organization criteria for AIDS and considered late in the course of their illness; 98% had antibody to HIV by ELISA. All blood cultures were negative. These data suggest that disseminated infection with M. avium-intracellulare is infrequent in Ugandan patients with AIDS, if it occurs at all.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Strain- and donor-related differences in the interaction of Mycobacterium avium with human monocytes and its modulation by interferon-gamma.

Mycobacterium avium is a cause of disseminated infection in AIDS patients. The pathogenicity of M. avium for human monocytes was examined in an in vitro model. Peripheral blood monocytes obtained from 13 healthy donors were precultured for 2 days before infection. Monocytes were infected with six AIDS-associated and three non-AIDS-associated strains and four strains of M. avium selected on the basis of colonial morphology. Uptake of M. avium detected by counting intracellular acid-fast bacilli differed according to colonial morphology: Bacteria with round and opaque colony forms were phagocytosed more readily than those with flat colonies. Virulence as defined by intracellular growth was also partly associated with colonial morphology. Some but not all bacilli with flat colony forms multiplied in human monocytes; strains of the round opaque colonial form did not. The effects of recombinant human interferon-gamma on M. avium infection also were examined. Pretreatment of monocytes suppressed phagocytosis. After infection, coculturing usually augmented mycobacterial growth inhibition by human monocytes, but these effects were variable from strain to strain. Overall, interferon-gamma produced a small but statistically significant inhibition of intracellular growth in three of four strains tested.

Acquired Immunodeficiency Syndrome↗
PubMed1990

UVB radiation and human monocyte accessory function: differential effects on pre-mitotic events in T-cell activation.

Purified T lymphocytes fail to proliferate in response to antigenic and mitogenic stimuli when cultured in the presence of accessory cells that have been exposed in vitro to sublethal doses of UVB radiation. Because proliferation represents a final stage in the T-cell activation process, the present study was conducted to determine whether T cells were able to progress through any of the pre-mitotic stages when UVB-irradiated monocytes were used as model accessory cells. In these experiments, monoclonal anti-CD3 antibodies were employed as the mitogenic stimulus. Culture of T cells with UVB-irradiated monocytes did allow the T cells to undergo an increase in intracellular free calcium, which is one of the first steps in the activation sequence. The T cells expressed interleukin-2 receptors, although at a reduced level. However, T cells failed to produce interleukin-2 above background levels when they were placed in culture with monocytes exposed to UVB doses as low as 50 J/m2. Incubation of T cells with UVB-irradiated monocytes did not affect the subsequent capacity of T cells to proliferate, since they developed a normal proliferative response in secondary culture when restimulated with anti-CD3 antibodies and unirradiated monocytes. These studies indicate that T lymphocytes become partially activated when cultured with UVB-irradiated monocytes and mitogenic anti-CD3 monoclonal antibodies. In addition, they suggest that interleukin-2 production is the T-cell activation step most sensitive to inhibition when UVB-irradiated monocytes are employed as accessory cells.

Antigens, CD↗
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↗
PubMed1990

Expression of functional interleukin 2 receptors by peripheral blood monocytes from patients with active pulmonary tuberculosis.

Peripheral blood monocytes from patients with active tuberculosis are "activated" by a number of criteria, including selective depression of T-lymphocyte responses to the mycobacterial antigen, tuberculin-purified protein derivative (PPD). We studied monocytes from patients with tuberculosis and healthy skin test reactive controls for expression and function of IL 2 receptors (IL 2R). Depletion of adherent monocytes increased the IL 2 activity of supernatants of PPD-stimulated T cell cultures from patients by 30-fold. When cultured with purified IL 2, adherent cells from the patients depleted IL 2 activity by 66%. Monocytes from patients displayed IL 2R on their surface as evidenced by anti-Tac reactivity, and released soluble IL 2R into the medium during culture. The release of soluble IL 2R was augmented when monocytes were cultured with PPD. Finally, freshly isolated adherent monocytes from patients but not healthy individuals expressed the gene encoding Tac protein. Thus, blood monocytes from patients with tuberculosis express functional IL 2R constitutively. This property may be important in the immunoregulatory and effector function of mononuclear phagocytes during tuberculosis.

Blotting, Northern↗
PubMed1990

Dissociation of immunoregulatory function of blood monocytes from maturational state and expression of interleukin-1 in humans chronically infected with Schistosoma mansoni.

We investigated the immunoregulatory function and properties of monocytes in 54 S. mansoni infected Egyptians (40-3,840 S. mansoni eggs excreted per gram of stool) 13-35 years of age. Adherent cell-mediated suppression was found in 11 of 36 patients. Cytochemical studies and reactivity with monoclonal antibodies directed at differentiation markers failed to show alterations in the distribution or maturation of monocytes. Peripheral blood mononuclear cells (PBMC) from these individuals produced lower levels of interleukin-1 (IL-1) in response to bacterial lipopolysaccharide and Staphylococcus albus stimulation as compared to the other S. mansoni infected individuals. Overall, IL-1 production by PBMC stimulated with LPS or Staphylococcus albus was higher in infected individuals compared to uninfected controls and correlated with intensity of infection (r = 0.41, P = 0.002 for LPS; r = 0.45, P = 0.006 for S. albus). IL-1 expression by monocytes from individuals with heavy S. mansoni infection exceeded that of subjects with light infection. The intensity-related increase in IL-1 expression did not correlate with the maturational state or the immunoregulatory properties of the monocytes.

Adolescent↗