Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytokines such as interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are important in normal immune processes. In this study, we demonstrate that human immunodeficiency virus type 1 (HIV-1) virions induce normal peripheral blood mononuclear phagocytes to produce both IL-1 and TNF within a few hours after their exposure to virus. The induction of these cytokines by HIV-1 does not require a productive infection. Blocking studies with soluble CD4 indicate that the effect is mediated through the CD4 molecule. In addition, the treatment of mononuclear phagocytes with OKT4A monoclonal antibody mimics the effects of HIV-1. Thus, these results indicate that induction of IL-1 and TNF alpha can occur via signals mediated through the CD4 molecule on mononuclear phagocytes. TNF has been shown by other investigators to induce HIV-1 expression. Therefore, TNF alpha may play a role in autocrine and paracrine regulation of HIV-1 expression. In addition, the induction of IL-1 and TNF by HIV-1 may also contribute to some of the neurologic and physiologic disorders associated with acquired immunodeficiency syndrome.
 ...
PMID:Interleukin-1 and tumor necrosis factor alpha can be induced from mononuclear phagocytes by human immunodeficiency virus type 1 binding to the CD4 receptor. 278 93

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.
 ...
PMID:Alveolar CD8+CD57+ lymphocytes in human immunodeficiency virus infection produce an inhibitor of cytotoxic functions. 751 68

Recent progress in the definition of molecules involved in immune regulation has led to the discovery of a number of type I membrane glycoproteins with a distinctive, cysteine-rich, repetitive domain structure within their extracellular regions. Because the prototype members of this family are receptors for cytokines (tumor necrosis factor [TNF] and nerve growth factor [NGF]), it was expected that the ligands for the other receptors would possess cytokine-like activities. This prediction has been fulfilled by the cloning of cDNA encoding a series of type II membrane glycoproteins, with homology to TNF, that bind to, and signal through, their cognate receptors. While the biological role of some of these ligand-receptor pairs remains obscure, at least two members of the family, CD40 and Fas, have proven their importance. The human X-linked immunodeficiency, hyper IgM syndrome, is the result of mutations in the CD40 ligand gene, and the Fas and Fas ligand genes are mutated in two mouse strains, lpr and gld, that develop autoimmune disease. These findings, together with other evidence, point to key roles of CD40/CD40 ligand interactions in immune activation, particularly in T-dependent B cell responses, and of Fas/Fas ligand in apoptosis and peripheral tolerance. These molecules, as well as the other ligands of the family, share the property of costimulation of T cell proliferation and are all expressed by activated T cells. More detailed analysis of the expression patterns of ligands and receptors on lymphocyte subpopulations will be necessary to define their different roles in immune activation and suppression.
 ...
PMID:A family of ligands for the TNF receptor superfamily. 752 88

In this study we have raised spontaneous Epstein-Barr virus (EBV)-positive lymphoblastoid cell lines (LCL) from the peripheral blood of human immunodeficiency virus (HIV)-infected individuals and of control patients with primary EBV infections. These LCLs were also raised in the presence of the viral inhibitor phosphonoformate (PFA); under these conditions, the in vitro infection of bystander B lymphocytes with EBV released in culture by in vivo infected B cells is inhibited. Thus, the latter LCLs are likely to represent the progeny of B cells latently infected by EBV in vivo. The LCLs raised in the presence or absence of PFA had the same phenotypic features, type of EBV latency, and growth pattern irrespective of whether they had been raised from HIV-seropositive individuals or patients with primary EBV infections or had been generated by infecting normal B cells in vitro. Studies on the production of inflammatory cytokines were conducted by Northern blotting or by determining the cytokine concentrations in the cell supernatants by immunoassays or bioassays. Three of eight LCLs from HIV-seropositive patients released TNF alpha and 5/5 released TNF beta, IL6 was present in the supernatants of 1/8 LCLs, and IL1 alpha and IL1 beta were not detected in any culture supernatant. No differences were noticed in the patterns of cytokine secretion among the LCLs from HIV-seropositive patients and in those raised from patients with primary EBV infections or obtained by infecting normal B cells in vitro with EBV. It is tempting to speculate that abnormally expanded EBV-harboring B cells in HIV-seropositive patients may participate in the pathogenesis of certain clinical manifestations by releasing inflammatory cytokines; some of these cytokines might also contribute to the in vivo spreading of HIV infection. However, the spontaneous LCLs from HIV-seropositive individuals do not display abnormal features compared to latently EBV-infected LCLs from other sources despite the high frequency of EBV-driven lymphoproliferative disorders observed in AIDS patients.
 ...
PMID:Production of inflammatory cytokines by Epstein-Barr virus (EBV)-infected lymphoblastoid cell lines spontaneously originated from the peripheral blood of patients with human immunodeficiency virus (HIV) infection. 758 23

Hyperimmunoglobulin E syndrome (HIES) is a rare immunodeficiency disorder characterized by increased serum immunoglobulin E levels. Bone fragility is part of this syndrome, which has recently been reported to be also associated with an imbalance in cytokine-secreting lymphocyte subpopulation. It has recently been shown that some cytokines can play a role in the bone fragility following menopause. We therefore investigated six patients (mean age 16.5 +/- 8.5 years) affected by this rare syndrome in order to study their bone remodeling and the possible involvement of cytokines in causing the bone fragility associated with this disease. Three of six patients had suffered long bone fractures; in four of six patients the cortical bone mass measured at the distal radius was two standard deviations below that of the aged-matched controls. Urinary pyridinoline excretion, a marker of bone resorption, was markedly increased in the two youngest patients. Adherent mononuclear cells derived from these patients were cultured in vitro and the bone resorbing activity (BRA) of the culture supernatant was measured by means of a fetal rat long bone assay. The BRA was up to 28% above the basal value. We compared the BRA and the cytokine production by the mononuclear cells of these patients to that of postmenopausal women. The BRA, and the IL1 beta, IL6, and TNF alpha levels in the mononuclear cell culture supernatants were identical for both HIES and postmenopausal women. However, the levels of PGE2 were higher and the levels of interferon-gamma were lower in the HIES patients. In conclusion, increased bone resorption in young patients with the HIES is responsible for the cortical bone loss that leads to a higher incidence of fractures. The high BRA secreted by the mononuclear cells of these patients is similar to that found in mononuclear cells from postmenopausal women. These data provide evidence of potent mononuclear cell activation leading to bone loss in HIES, which could be related to IgE-dependent mechanisms.
 ...
PMID:Cytokine-mediated bone resorption in patients with the hyperimmunoglobulin E syndrome. 760 71

The effects of cysteamine (2-aminoethanethiol, MEA) and its disulfide, cystamine, on the human immunodeficiency virus (HIV-1) expression in chronically infected promonocytic cells (U1), T cell line (ACH-2), and peripheral blood monocyte-derived macrophages (MDM) were investigated. U1 and ACH-2 cells constitutively express low levels of virus, which is increased by the addition of tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and other inducers. Cystamine, in noncytotoxic doses, suppressed in a concentration-dependent fashion the induction of HIV-1 expression mediated by TNF-alpha, IL-6, GM-CSF, and monokine-enriched monocyte culture supernatants in both U1 and ACH-2 cells as determined by HIV-1 reverse transcriptase (RT) activity. Similarly, HIV-1 expression was substantially reduced in the cystamine-treated primary MDM cultures compared with the untreated control cultures. The addition of cystamine into HIV-1 chronically infected MDM (12 days after infection was established) also suppressed 80-90% of RT activity in comparison to the untreated controls. HIV-1 (Bal) infected MDM cultures (without cystamine treatment) demonstrated giant syncytium formation, whereas cystamine-treated cultures lacked the giant syncytia induced by HIV-1 infection. Cystamine also inhibited LPS-induced TNF production in MDM. In contrast to cystamine, cysteamine showed no significant effects on either the monokine-induced HIV-1 expression in U1 or ACH-2 or acute and chronic HIV-1 infection in MDM.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cystamine inhibits HIV type 1 replication in cells of monocyte/macrophage and T cell lineages. 763 61

We have previously shown chronic immune activation and enhanced generation of reactive oxygen species in common variable immunodeficiency (CVI). In the present study, we examined levels of glutathione, the dominant intracellular thiol, that play an important protective role against oxidative and inflammatory stress in plasma and in monocytes and lymphocyte subsets in 20 CVI patients and in 16 healthy controls. CD4+ lymphocytes from CVI patients had significantly lower levels of both total and reduced glutathione as well as a lower ratio of reduced to total glutathione compared with healthy controls. This decrease in glutathione levels in CD4+ lymphocytes was most pronounced in the CD45RA+ subset. Plasma levels of total glutathione were also significantly decreased in CVI. In contrast, monocytes from CVI patients exhibited increased levels of both total and reduced glutathione compared with blood donor monocytes. CVI patients had significantly raised serum levels of tumor necrosis factor alpha (TNF alpha) and TNF alpha concentration was strongly associated with glutathione depletion in CD4+ lymphocytes. Furthermore, the lowest levels of both total and reduced glutathione were found in a subgroup of CVI patients characterized by persistent immune activation in vivo, decreased numbers of CD4+ lymphocytes in peripheral blood, and splenomegaly. Finally, supplementation of cell cultures with glutathione-monoethyl ester did significantly enhance interleukin-2 production from peripheral blood mononuclear cells in CVI patients. These glutathione abnormalities in CVI indicate increased oxidative stress, particularly in CD4+ lymphocytes, and intracellular depletion of reduced glutathione of the demonstrated magnitude may have profound implications for CD4+ lymphocyte function and the immunodeficiency in CVI.
 ...
PMID:Decreased levels of total and reduced glutathione in CD4+ lymphocytes in common variable immunodeficiency are associated with activation of the tumor necrosis factor system: possible immunopathogenic role of oxidative stress. 763 46

The inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) has been shown to stimulate human immunodeficiency virus type 1 (HIV-1) replication in both chronically and acutely infected T lymphocytes and monocytes. Transcriptional activation of the HIV long terminal repeat and subsequent increase in virus production are linked to TNF activation of the cellular transcription factor NF-kappa B. Here we report the use of two forms of soluble recombinant type 1 (p80) TNF receptor to inhibit TNF-induced HIV activation in vitro. One receptor form is a monomer containing the entire 236 residues of the extracellular (ligand-binding) portion of p80. A second receptor form is a chimeric homodimer containing these residues fused to a truncated human IgG1 immunoglobulin heavy chain and, thus, resembles a bivalent antibody without light chains. These recombinant receptor proteins were tested for their ability to inhibit TNF-alpha-induced expression of HIV-1 in chronically infected human cell lines. We also examined the ability of the soluble receptors to limit the activation of the HIV-long terminal repeat transcription. The soluble TNF receptor dimer was most effective at blocking TNF-alpha-induced HIV-1 expression in both monocytoid and lymphoid cells. The molar ratio of TNF-receptor dimer to TNF-alpha found to be most effective was, at least, 5:1. We conclude that at specific TNF/soluble TNF-receptor dimer ratios, TNF-alpha-induced HIV-1 transcription and expression can be limited in vitro.
 ...
PMID:Soluble tumor necrosis factor receptor: inhibition of human immunodeficiency virus activation. 768 92

Phagocytosis of Mycobacterium tuberculosis by human monocytes or macrophages is classically followed by granuloma formation in vivo. Granuloma are comprised of cells of the monocyte lineage together, in many instances, with antigen-specific T lymphocytes. Development of granuloma depends upon recruitment of both cell types, but recruitment of monocytes is pivotal as these cells secrete anti-mycobacterial cytokines and IL-8, a T cell chemoattractant. We have therefore investigated gene regulation of Monocyte Chemotactic Protein 1 (MCP-1), an important monocyte chemotactic cytokine, following phagocytosis of particulate material (latex beads and zymosan) and live M. tuberculosis by two human monocytic cell lines. In THP-1 cells and phenotypically more differentiated Mono Mac 6 cells, MCP-1 mRNA accumulation was first detectable by Northern analysis of 4 hours and increased over 24 hours. Magnitude and kinetics of MCP-1 gene expression was independent of the biochemical nature of the phagocytic stimulus, M. tuberculosis strain virulence or pre-treatment with anti-TNF. In contrast to the uniform effect of different phagocytic stimuli on MCP-1 gene expression, we have shown that M. tuberculosis but not latex or zymosan, increased IL-8 gene expression, a chemotactic agent for T cells. In additional experiments with THP-1 cells infected with human immunodeficiency virus (HIV), viral infection did not alter MCP-1 gene expression following phagocytosis. MCP-1 gene expression appears to be a conserved antigen-independent response of human monocytic cells which is activated following particulate phagocytosis. MCP-1 gene expression may thus be involved in recruitment of monocytes during granuloma formation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Phagocytosis of Mycobacterium tuberculosis or particulate stimuli by human monocytic cells induces equivalent monocyte chemotactic protein-1 gene expression. 768 73

In patients with chronic renal failure alterations in monokine production are a common feature. Their clinical relevance has not yet been proven. We show here a correlation between an overproduction of interleukin-(IL)-6 and tumor necrosis factor alpha (TNF alpha) upon stimulation with LPS by mononuclear cells in vitro and the clinical grade of immunodeficiency found in these patients. Higher levels of IL-6 and TNF alpha were correlated with an immunocompromized state, that is, non-responsiveness to hepatitis B vaccination, whereas patients with a better immune competence showed the same levels of these cytokines as healthy controls. Only the patients with a good immune function showed a high secretion of IL-10. The feedback mechanism of IL-10 for reducing monokine synthesis seems to be intact in these patients. Thus the secretion of IL-10 might be regarded as a compensatory mechanism which controls monokine induction by chronic renal failure and hemodialysis treatment. Immunocompromized patients who are unresponsive to hepatitis B vaccination seem to be unable to enhance IL-10 synthesis for control of monokine overproduction. This results in higher levels of IL-6 and TNF alpha that might be involved in the pathogenesis of reduced immune defense.
 ...
PMID:Production of interleukin-6, tumor necrosis factor alpha and interleukin-10 in vitro correlates with the clinical immune defect in chronic hemodialysis patients. 772 41


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>