Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The production of interleukin-2 (IL-2) by Con A-activated spleen cells (SC) progressively declined and reached negligible values during the course of infection of C57BL/6 mice with Mycobacterium lepraemurium. In addition, the capacity of cultured SC to utilize IL-2 was highly reduced, as demonstrated by the accumulation of IL-2 activity in culture supernatants at 48 and 72 h after Con A activation. The depressed IL-2 utilization started to be observed about 1 to 2 weeks prior to the onset of the depressed IL-2 production and was not reversed by the addition of exogenous IL-2; thus implying that a lack of IL-2 utilization rather than a lack of IL-2 production could be directly responsible for the inhibition of T-cell proliferative responses to Con A in SC cultures of infected mice. The utilization of IL-2 was found to be down-regulated, at least in part, by splenic suppressor cells since, in mixed-culture experiments, SC from infected mice actively depressed the capacity of normal splenocytes to consume IL-2. Finally, the depressed IL-2 utilization would result from a 2- to 3-fold reduction of either or both the density of high-affinity IL-2 receptors and their affinity for IL-2.
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PMID:Unresponsiveness to Con A in spleen cell cultures of M. lepraemurium-infected mice is dependent on a defective expression of high-affinity IL-2 receptors rather than on a lack of IL-2 production. 266 Oct 60

The results shown here demonstrate that in mice heavily infected with Mycobacterium bovis BCG Pasteur, mitogen-induced levels of interleukin-2 (IL-2) correlate temporally with the state of immunity that is being expressed in the animal during the course of the infection. Active immunity, which is conferred by populations of both CD4+ (L3T4) and CD8+ (Lyt-2) T lymphocytes, and memory immunity, which is mediated by a population of CD4+ T lymphocytes, were identified and distinguished in terms of their sensitivity to cyclophosphamide therapy, their ability to passively transfer specific resistance to infection with virulent Mycobacterium tuberculosis, and their capacity to produce and/or absorb IL-2. In this regard, concanavalin A (Con A)-stimulated L3T4+ and Lyt-2+-enriched splenocytes exhibited an apparent depression in measurable levels of IL-2 when harvested during the first 40 days of the infection, which could be explained by the subsequent observation that these T cells were capable of rapidly absorbing a known quantity of recombinant IL-2 in vitro. Detectable levels of IL-2 in these mitogen-stimulated supernatants began to rise after Day 25, which was temporally associated with a gradual shift from active immunity, to immunity mediated by cyclophosphamide-resistant memory T cells, which did not absorb IL-2 in vitro. These data indicate that fluctuations in apparent IL-2 production reflect changes in the type of immunity being expressed, rather than than some form of defect in IL-2 production.
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PMID:Patterns of IL-2 production and utilization in mice heavily infected with Mycobacterium bovis BCG reflect the phase of protective immunity being expressed. 266 9

Inbred strain 2 guinea pigs were vaccinated with Mycobacterium bovis BCG or were left unvaccinated. They were maintained for 6 weeks on defined, isocaloric diets containing either 30% (control animals) or 10% (animals receiving low protein) ovalbumin as the sole protein source. Animals were challenged by the respiratory route with a low dose of virulent M. tuberculosis H37Rv and killed 4 weeks later. Protein-malnourished animals were not protected by previous vaccination with BCG. Lymphocytes isolated from various tissues were tested in vitro for proliferative responses to mitogen (concanavalin A) and antigen (purified protein derivative [PPD]), production of interleukin-2 (IL-2), and response to exogenous recombinant IL-2 (rIL-2). Protein-malnourished guinea pigs responded only weakly to PPD skin tests, and their blood and lymph node lymphocytes exhibited impaired proliferation when cultured with PPD in vitro. IL-2 levels were consistently low in cultures of stimulated blood and spleen lymphocytes from protein-deprived animals. BCG vaccination of nutritionally normal guinea pigs, on the other hand, induced significantly more IL-2 production by PPD- and concanavalin A-stimulated lymphocytes. The addition of exogenous mouse rIL-2 (40 and 80 U/ml) in vitro to PPD-stimulated blood and lymph node cells from nonvaccinated, protein-deprived guinea pigs resulted in no improvement of the proliferative response. Previous vaccination of malnourished guinea pigs did not consistently enhance the response of PPD-stimulated lymphocytes to added rIL-2. Dietary protein deficiency and BCG vaccination appear to modulate antigen-driven cellular immunity in animals with tuberculosis by altering the production of, and the response to, IL-2 by PPD-stimulated lymphocytes.
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PMID:Dietary protein deficiency and Mycobacterium bovis BCG affect interleukin-2 activity in experimental pulmonary tuberculosis. 278 35

A mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate (GaGM), derived from Gordona aurantiaca, an acid-fast bacterium closely related taxonomically to Mycobacterium, was investigated for its immune adjuvant activity on cell-mediated responses in the mouse. I.V. injection of liposomes containing GaGM enhanced the generation of cytotoxic T-lymphocyte (CTL) against syngeneic and allogeneic tumor cells. In addition, the injection of GaGM augmented the natural killer (NK) activity and the antibody-dependent cellular cytotoxicity (ADCC). These results suggest that the injection of GaGM induces the production of interleukin-2 (IL-2), since such effector cells as CTL, NK and K cells have been shown to require IL-2 for their development.
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PMID:[An immune adjuvant activity of mycolic acid-containing glycolipid, trehalose-2,3,6'-trimycolate, derived from Gordona aurantiaca]. 278 54

T-cell clones capable of mounting a proliferative response to Mycobacterium leprae were obtained in three leprosy patients (two polar lepromatous and one polar tuberculoid) either from M. leprae-activated or from protein-purified derivative-activated polyclonal T lymphoblasts. All these clones expressed the CD4 surface marker. Some of them proliferated to the antigen only in the presence of interleukin-2. A majority expressed cross-reactive responses to other mycobacteria. Clones obtained from the lepromatous patients did not differ in any of these features from those obtained from the tuberculoid patient. M. leprae-reactive clones obtained from one lepromatous patient displayed strong antigen-specific cytotoxicity toward autologous antigen-coated target cells. This phenomenon was not observed for any clone of the other lepromatous patient and was seen only for one clone in the tuberculoid patient.
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PMID:Mycobacterium leprae-reactive T-cell clones isolated from polar lepromatous and tuberculoid leprosy patients. 283 Aug 93

Mycobacterium-avium complex (MAC) is an intracellular pathogen and the most common cause of widely disseminated bacterial infection in patients with the acquired immunodeficiency syndrome (AIDS). MAC is infrequently seen in other immunocompromised adults, suggesting that the host defense defect allowing for MAC infection is relatively unique for AIDS. A system was developed for studying the immune response to MAC infection, utilizing MAC isolated from patients with AIDS and monocytes from normal controls and patients with AIDS. Phagocytosis, superoxide anion (SOA) production, and killing were measured. Monocytes from normal controls and AIDS patients were identical with respect to phagocytosis of MAC. In contrast, baseline SOA production was elevated in monocytes from patients compared to normal monocytes and was minimally augmented in response to either phorbol myristate acetate or MAC. Fourteen-day kinetic studies revealed in patients and controls a biphasic pattern with 50-99% killing of AIDS-derived MAC initially, followed always by a rapid outgrowth of surviving bacilli. Despite a modest enhancement of MAC killing by normal but not patients' monocytes pretreated with either recombinant interferon-gamma or recombinant tumor necrosis factor-alpha, outgrowth of MAC was always observed in both, typically faster in patients than in controls. Even monocytes in the presence of lymphocytes stimulated with interleukin-2 did not demonstrate enhanced MAC killing. In contrast, high-titered anti-MAC immune serum derived from a patient with polymyositis and disseminated MAC significantly enhanced the killing of MAC by monocytes from both AIDS patients and healthy controls and prevented their outgrowth. These findings suggest that the host defense defect allowing for MAC infection appears not to reside in the monocyte and that the in vitro lymphocyte functions examined in this study do not appear to play a major role. What role specific antibody plays in vivo in preventing disseminated MAC is uncertain, but the lack of such antibody may help explain the propensity for AIDS patients to develop systemic infection.
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PMID:Host defense against Mycobacterium-avium complex. 284 66

BALB/c mice were infected with Mycobacterium lepraemurium (MLM) in the foot pad or with M. bovis BCG intravenously with 5 x 10(7) bacilli. Recombinant interleukin-2 (IL-2) was injected intraperitoneally as a single dose (20,000 u), single course of 5 injections (400 u each) or 6 monthly courses starting 3 days or 60 days after the MLM infection. BCG infected mice received a single dose (1000 u) or 5 daily injections of 100 or 1000 u each. IL-2 significantly reduced the total bacterial counts in the footpad, lymph node and liver of MLM infected mice (50-85%) by 6 months and viable counts in the spleen (30-50%) by 60 days after BCG infection. The courses of IL-2 started at 60 days were more effective than at 3 days after MLM infection (P less than 0.05-0.001) and in the case of BCG, 100 u of IL-2 was better than 1000 u (P less than 0.05-0.01). These results indicate that IL-2 limits mycobacterial infections in mice, and raise the question of its possible use in humans.
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PMID:Recombinant interleukin-2 limits the replication of Mycobacterium lepraemurium and Mycobacterium bovis BCG in mice. 304 14

Mice were infected intravenously with 1.0 mg of Mycobacterium bovis BCG. At various times thereafter, spleen and peripheral lymph node cells were stimulated with concanavalin A for 18 to 20 h, and their capacity to produce interleukin-2 (IL-2) was evaluated by means of a T-cell blast proliferation technique. A depression of IL-2 production that was complete in the spleen but partial in lymph node cell cultures occurred at 2 to 3 weeks and persisted till weeks 8 to 10 after infection. No direct evidence was found for an active suppressor mechanism depressing in vitro the production of IL-2. In spleen cell cultures the suppression of IL-2 production would result from a functional defect of the IL-2-producing T-cell subset, whereas in lymph node cell cultures the depression mainly results from a relative lack of IL-2-producing cells caused by an accumulation of immunoglobulin-positive and "null" cells. Spleen cells from BCG-infected mice maintained their capacity to acquire IL-2 receptors when activated by concanavalin A.
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PMID:Mechanisms underlying the depressed production of interleukin-2 in spleen and lymph node cell cultures of mice infected with Mycobacterium bovis BCG. 308 45

T-cell clones were established from Mycobacterium tuberculosis-immunized mice. These clones had the phenotype Thy-1+ L3T4+ Lyt-2- and were restricted by the H-2I-A locus. After antigen stimulation, the T-cell clones secreted interleukin-2 and gamma interferon. Factors produced by these T-cell clones activated normal bone marrow macrophages for antimycobacterial activity in vitro. Furthermore, the T-cell clones could adoptively confer delayed-type hypersensitivity on normal recipient mice. These findings indicate that the T-cell clones clones expressed relevant functions of antimycobacterial immunity. The antigen reactivity of the T-cell clones to different mycobacterial species ranged from broad cross-reactivity to stringent specificity, and none of the clones distinguished between M. tuberculosis and M. bovis. Thus, M. tuberculosis-immune helper/inducer T cells of identical phenotype, genetic restriction, and function varied in their antigen specificity. T-cell clones of the type described will facilitate functional characterization of mycobacterial antigens on the T-cell level.
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PMID:Function and antigen recognition pattern of L3T4+ T-cell clones from Mycobacterium tuberculosis-immune mice. 309 37

Mice were immunized intradermally with 10(7) irradiated Mycobacterium leprae organisms, and draining lymph nodes were collected after 4 weeks. Lymph node cells were restimulated in vitro with soluble M. leprae antigen and accessory cells. The resulting T-cell line was propagated in vitro in the presence of M. leprae antigen, accessory cells, and interleukin-2-containing supernatants from concanavalin A-stimulated rat spleen cells. Long-term cultured T cells were Thy-1+ L3T4- Lyt-2+ as revealed by analysis with the fluorescence-activated cell sorter. From this line, T-cell clones with the same phenotype were established. The T-cell clone A4 failed to secret interleukin-2 after stimulation with antigen and accessory cells, and its growth depended on exogeneous interleukin-2. A4 T cells produced gamma interferon in an antigen-specific, H-2-restricted, and interleukin-2-dependent way. Importantly, this T-cell clone was capable of lysing bone marrow macrophages presenting M. leprae antigen. Other T-cell clones as well as native Lyt-2+ T cells from M. leprae-immunized mice were also capable of lysing bone marrow macrophages expressing M. leprae antigens. These findings suggest that specific Lyt-2+ T cells participate in the immune response to M. leprae. It is postulated that cytolysis of M. leprae-infected macrophages or Schwann cells contributes to protection against and pathogenesis of leprosy.
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PMID:Mycobacterium leprae-specific Lyt-2+ T lymphocytes with cytolytic activity. 309 92


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