UMLS:C0021051 - FACTA Search

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood monocytes from human immunodeficiency virus (HIV)-infected individuals or AIDS-related complex/AIDS patients ex vivo exhibit distinct alterations in some but not all immune functions. In studies presented here, monocytes from healthy donors were infected with HIV 1 in vitro and co-cultures with autologous uninfected T lymphocytes were set up. The monocyte/macrophage (M phi)-dependent T cell function was determined by measurement of proliferative and secretory [interleukin (IL)2, interferon-gamma] responses to lectin (phytohemagglutinin), mitogen (anti-CD3 monoclonal antibody), or recall antigen (tetanus toxoid, tuberculin). Accessory function of M phi was normal after HIV infection when optimal amounts (10%-20%) were added to the T lymphocytes. However, HIV infection of M phi significantly decreased T cell proliferative responses and secretion of IL2 when supplemented at limited dilution (0.5%-5%), although interferon-gamma production was not affected. Whereas the lipopolysaccharide-triggered M phi production of IL1 was not impaired by HIV 1 infection, there was a significant decrease in this response when anti-CD3 monoclonal antibody or tetanus toxoid were used to trigger the peripheral blood mononuclear cells. The impairment of proliferation of T lymphocytes in the presence of HIV 1-infected M phi could be overcome by addition of exogenous IL 1. Taken together, these data clearly show that the mononuclear phagocyte-dependent enhancement of stimulated T cell proliferation and lymphokine secretion is decreased when the restricted numbers of monocytes/M phi are HIV 1 infected. There are, therefore, two possible roles of M phi in HIV infection and progression to disease. First, as a reservoir and vehicle for dissemination of the virus, and second, as an immune cell whose essential functions are impaired by infection.
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PMID:Decreased accessory cell function of macrophages after infection with human immunodeficiency virus type 1 in vitro. 225 85

Our data demonstrate that the epithelial component of the human thymic microenvironment is not an inert cell type, but rather is capable of being directly involved in the promotion of both early and late stages of T-cell maturation. Data from our laboratory [54,69], together with the work of Plunkett et al. [61] and Shaw et al. [70] suggest that an endogenous ligand for the CD2 molecule in humans is the LFA-3 molecule. Using an SV40 transformed human thymic epithelial cell line of subcapsular cortical origin, Mizutani et al. have confirmed that thymic epithelial cells bind thymocytes via a CD2/LFA-3 interaction [78]. The data reviewed in this paper suggest that within the thymus one endogenous ligand for the alternative pathway of thymocyte activation via the CD2 molecule is the LFA-3 molecule on TE cells. Following thymocyte binding to TE cells, immature thymocytes are directly activated to proliferate, and their response to both IL1 and IL2 is augmented. Also, following TE-thymocyte binding, TE-IL1 secretion is augmented and TE cell MHC class II antigen expression is induced. Moreover, while undergoing activation, thymocytes appear to be able to modulate their microenvironment milieu of MHC antigens and IL1. Further analysis of the sequelae of TE-thymocyte interactions using phenotypic characterization of thymocytes with anti-T-cell MoAbs, coupled with molecular analysis of thymocyte T-cell receptor genes, should allow for the determination of the precise sequential stages that immature T cells undergo enroute to functional maturity. Understanding these steps in T-cell maturation will be critical to our understanding of the events that transpire in the genesis of autoimmune, lymphoproliferative, and immunodeficiency diseases.
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PMID:Epithelial-thymocyte interactions in human thymus. 350 Jan 57

Four patterns of structural alterations were found in lymph nodes (LNs) from rhesus monkeys 17 to 34 months after infection with simian immunodeficiency virus (SIV-mac251). SIV p27gag antigen and viral particles were localized either between the processes of follicular dendritic cells (FDCs) or in the cytoplasm of macrophages. In hyperplastic follicles, enlarged germinal centres contained numerous Ki67+ proliferating centroblasts which were rather rare in light zones occupied by the CD23+ FDC network. Involuted follicles contained a small number of Ki67+ centroblasts and the CD23 labelling was limited to a very small apical zone. A correlation was found between the morphological characteristics of the follicles (hyperplasia-involution) and the level of expression of the vascular cell adhesion molecule 1 (VCAM1) on FDCs. A gradient in VCAM1 intensity with no expression in the subcapsular-intermediary sinuses, low membrane labelling in the mantle and strong expression in the FDC network was observed. IL1 alpha+ and IL6+ (interleukin) cells (lymphocytes and macrophages) were detected in the mantle, the interfollicular area and the medulla of LNs. Expression of the tumour necrosis factor alpha and ultrastructural markers of interferon alpha production were found in a few FDC and macrophages. Our findings indicate a close relationship between the morphofunctional properties of FDC and the LN structure in SIV infection.
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PMID:Morphological changes in lymph nodes and expression of VCAM1 and cytokines at the late stages of SIV-induced disease in rhesus monkeys. 748 Oct 91

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.
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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.
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PMID:Cytokine-mediated bone resorption in patients with the hyperimmunoglobulin E syndrome. 760 71

Perhaps as many as 25-50% of adult patients and children with acquired immunodeficiency syndrome (AIDS) eventually suffer from neurological manifestations, including dysfunction of cognition, movement, and sensation. How can human immunodeficiency virus type 1 (HIV-1) result in neuronal damage if neurons themselves are for all intents and purposes not infected by the virus? This article reviews a series of experiments leading to a hypothesis that accounts at least in part for the neurotoxicity observed in the brains of AIDS patients. There is growing support for the existence of HIV- or immune-related toxins that lead indirectly to the injury or demise of neurons via a potentially complex web of interactions among macrophages (or microglia), astrocytes, and neurons. HIV-infected monocytoid cells (macrophages, microglia, or monocytes), after interacting with astrocytes, secrete eicosanoids, i.e., arachidonic acid and its metabolites, including platelet-activating factor. Macrophages activated by HIV-1 envelope protein gp120 also appear to release arachidonic acid and its metabolites. In addition, interferon-gamma (IFN-gamma) stimulation of macrophages induces release of the glutamate-like agonist, quinolinate. Furthermore, HIV-infected macrophage production of cytokines, including TNF-alpha and IL1-beta, contributes to astrogliosis. A final common pathway for neuronal susceptibility appears to be operative, similar to that observed in stroke, trauma, epilepsy, neuropathic pain, and several neurodegenerative diseases, possibly including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves the activation of voltage-dependent Ca2+ channels and N-methyl-D-aspartate (NMDA) receptor-operated channels, and, therefore, offers hope for future pharmacological intervention. This article focuses on clinically tolerated calcium channel antagonists and NMDA antagonists with the potential for trials in humans with AIDS dementia in the near future.
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PMID:HIV-related neuronal injury. Potential therapeutic intervention with calcium channel antagonists and NMDA antagonists. 799 15

Wasted mice bear an autosomal recessive mutation (wst/wst) that manifests itself in neurologic abnormalities, immunologic deficiency, and faulty DNA repair evident by 21 days of age. The immunodeficiency is characterized by a reduction in the thymus-to-body weight ratio, low levels of IgA plasma cells at secretory sites, and increased sensitivity of T-cells to the killing effects of ionizing radiation. Experiments were designed to examine measures of T-cell activity in wasted mice. The initial experiments established that wst/wst mice have percentages of thymic and splenic Thy1+ cells equivalent to those of control littermates. Further studies of T-cell subpopulations with thymocytes revealed normal percentages of CD4+ and CD8+ cells in wst/wst mice; however, double-labeling experiments showed that CD8+ cells were predominantly CD4- in wst/wst mice, whereas in controls most CD8+ cells also expressed CD4+. Mesenteric lymph node T-cell subpopulations were similar in wasted and control mice. Because cytokines play a significant role in the regulation of the immune response and also interact with a variety of cellular systems, we examined the expression of different cytokine and related genes (IL1, IL2, IL2R, TNF, IL5, gamma-interferon, beta-TGF) in lymphoid tissues from wasted mice as well as from littermate and parental controls. Studies of RNA from lymphoid tissues of wasted mice using dot blot and Northern blot hybridizations revealed a deficiency of IL5 mRNA in thymus and spleen, decreased expression of IL2R in thymus (but not spleen), increased expression of IL1 in spleen (but not thymus), and increased expression of IL2, gamma-interferon, and beta-TGF in both spleen and thymus, relative to controls. Expression of TNF mRNA in lymphoid tissues was unaffected by the wasted mutation. These results suggest a role for cytokine imbalance in the pathogenesis of the immunodeficiency and other abnormalities of wasted mice.
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PMID:Cytokine and T-cell subset abnormalities in immunodeficient wasted mice. 803 37

This study evaluates the consequences of antiretroviral treatment of the acute simian immunodeficiency virus (SIV) primary infection on virus load and cytokine responses. Four cynomolgus macaques were inoculated intravenously with a pathogenic primary isolate (SIVmac251). Animals were pretreated with 10.8 mg/kg/day of dideoxyinosine (ddI) from 4 days before inoculation, and treatment was continued for 28 days. Proinflammatory (IL6, IL1 beta and TNF alpha) and antiinflammatory (IL10) cytokine and lymphokine (IL2, IL4 and IFN gamma) polymerase chain reaction (PCR) ratios were monitored in unmanipulated peripheral blood mononuclear cells (PBMCs) during acute infection by using a semiquantitative reverse transcription (RT)-PCR method. PBMC-associated virus loads were dramatically reduced compared to those of placebo-treated macaques. Nevertheless, a transient rise in IL6, IL1 beta, TNF alpha and IL10 mRNA expression was observed in PBMCs. IL2, IL4 and IFN gamma mRNAs were either undetectable or weakly detectable throughout the study, with no major changes. Despite a dramatic reduction in the acute viral loads in ddI-treated monkeys, early cytokine mRNA profiles were comparable to those of untreated SIVmac251-infected monkeys. Contrary to what was previously evidenced during primary infection with an attenuated SIV clone, no increase in IL2 and IL4 mRNA was detected in PBMCs of the ddI-treated monkeys, although these monkeys exhibited virus loads similar to those evidenced in macaques infected by attenuated SIV. These data indicate that differential lymphokine expression patterns found in pathogenic and Nef-truncated SIV-infected monkeys may not be strictly dependent on virus load levels.
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PMID:Consequences of ddI-induced reduction of acute SIVmac251 virus load on cytokine profiles in cynomolgus macaques. 992 10

Interleukin (IL)-1 family members are key players in inflammatory processes but have been the subject of few studies of acquired immunodeficiency syndrome (AIDS). To better evaluate the impact of the IL-1 family on AIDS development, we genotyped the IL1 alpha , IL1 beta , IL1Ra, and IL1R1 genes in 245 slow progressor (SP) and 82 rapid progressor (RP) human immunodeficiency virus type 1-seropositive patients as well as in 446 control subjects, all of whom were of white ethnicity. One hundred sixteen frequent polymorphisms were identified, of which 23 were newly characterized by our study. Many putative associations were found between single-nucleotide polymorphism (SNP) or haplotype alleles and the extreme profiles of progression. Most of them corresponded to weak associations (.01<P<.05); however, the SNP IL1Ra_2134 exhibited a consistent association, found at the level of the SNP, haplotypes, and haploblocks, when the SP and control populations were compared (P=.0002). The IL-1-dependent inflammatory response is, thus, likely to play a role in AIDS progression via the regulation of IL-1Ra expression. This association will need to be confirmed in other AIDS cohorts, and experiments will also have to be performed to unravel the biological mechanisms at work. The data presented here will be useful for future genomic studies of the IL-1 family members in other infectious and chronic inflammatory diseases.
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PMID:Exhaustive genotyping of the interleukin-1 family genes and associations with AIDS progression in a French cohort. 1708 30

The objective of the study was to determine the immunological characteristics of immunodeficiency and immunosuppression in children and to estimate the type of disorder within the immunological system. In the prospective study with 90 patients included, all were separated into three groups (30 patients per group) of which the first group was formed of patients with immunodeficiency; the second group of patients who were receiving the immunosuppressive therapy for autoimmune diseases for more than 6 months; and the third group being the control group formed of patients with uncomplicated bacterial infections. The follow-up parameters were gathered using questionnaire on personal and family anamnesis of patients with immunological parameters: humoral unspecific immunities (CRP, C3, C4, IL1 and IL2), humoral specific immunities (IgG, IgM, IgA and IgE) and cellular specific immunity. Concentrations of medium values of CRP in patients with immunodeficiency and on immunosuppressive therapy, statistically are significantly lower than in patients from the control group (p < 0.05). Individually increased concentrations of CRP within the groups are the indicator of acute inflammatory process and of relapse of basic disease in patients with autoimmune diseases. The concentrations of IL1 are lower than standard values in the test. in 28 patients (93%) with immunodeficiency and in 26 (87%) patients with immunosuppression. Increased concentrations in 2 (7%) patients with immunodeficiency are sign of acute inflammatory process, and 4 (14%) patients with immunosuppression and increased concentrations have shown signs of inflammation and relapse of basic disease. Concentration of IL2 in 1 (3%) patient from immunosuppressed group was increased (iatrogenic immunosuppressant). There is no statistically significant difference in concentrations of medium values of C3 and C4 complements among the studied groups of patients (p > 0.05). Concentrations of IgG in group of patients with immunodeficiency are statistically and significantly lower at medium and individual values (p < 0.001), as well as the concentrations of IgM and IgA (p < 0.05) comparing to other studied groups. Concentrations of IgE above 4.500 IU/ml were found in 3 (10%) patients with Hyper IgE syndrome. Results of our study have shown the possibility of evaluation of the level and the scale of disorder of the immunological system in children.
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PMID:[Humoral immunity in children with immunodeficiency and immunosuppression]. 1941 18

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