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

Following culture of human peripheral blood mononuclear cells (PBMNC) from 25 normal donors and 15 patients with common variable immunodeficiency (CVID), we were unable to identify any IL10-defective patients. Clear-cut effects of IL4 could be demonstrated in controls, while in CVID all effects are less pronounced. While in both controls and CVID baseline levels of IL6, IgG and IgM were found to be correlated, this was altered by the addition of either IL4 or Poke Weed Mitogen (PWM). We therefore conclude that the inability of PBMNC to produce IL10 is not the cause of CVID in our patients. In CVID, the regulating circuitry triggered by IL4 remains principally intact, however, some subgroups of CVID behave significantly differently.
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PMID:On interleukins 4, 6 and 10 and their interrelationship with immunoglobulins G and M in common variable immunodeficiency. 789 90

Feline immunodeficiency virus (FIV) is a lentivirus that induces an acquired immunodeficiency in domestic cats. The objective of this study was to compare the immune response of chronically FIV-infected cats and specific pathogen free (SPF) cats to Listeria monocytogenes, a facultative intracellular bacterium. Regional lymph nodes were removed at various times after subcutaneous inoculation with L. monocytogenes and evaluated. Lymph nodes of chronically FIV-infected cats enlarged more slowly and to a lesser degree than SPF cats. This was due to delayed and blunted lymphoid follicle formation and markedly diminished histiocyte influx. The cellular response correlated with a marked upregulation in IL10 transcription and delayed increase in TNF-alpha upregulation in FIV-infected cats. Transcriptional upregulation of IFN-gamma, IL4, and the p40 chain of IL12 was similar in lymph nodes of FIV-infected and SPF cats. Clinically, FIV-infected cats had a more severe response at the site of L. monocytogenes injection and showed signs of systemic bacterial dissemination while SPF cats remained clinically normal. FIV-infected cats generated a delayed hypersensitivity response similar to SPF cats but also had a significantly greater antibody response. Taken together, these data suggest excessive IL10 production may be responsible for the deficiency observed in the innate immune response of chronically FIV-infected cats challenged with L. monocytogenes.
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PMID:Effect of feline immunodeficiency virus on cytokine response to Listeria monocytogenes in vivo. 983 68

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

The demonstration that macrophages express CXCR4 has led to a reexamination of their susceptibility to human immunodeficiency (HIV)-1 X4 strains. Here, we examined the susceptibility to X4 HIV-1Lai of two previously characterized macrophage populations, obtained either as 1) adherent cells of five-day cultures of blood mononuclear cells (PBMC), followed by two days without nonadherent PBMC nor added cytokines (MDM-5d); or 2) as adherent cells recovered from one-hour incubation of PBMC, which were cultured for seven days with macrophage colony-stimulating factor (MDM-MCSF). Exposing MDM-5d or MDM-MCSF to HIV-1Lai did not lead to productive infection, as indicated by a lack of (MDM-MCSF) or low (MDM-5d) viral p24 levels in culture supernatants. However, MDM-5d vigorously transmitted HIV-1 Lai to autologous T lymphocytes, which was not the case of HIV-1Lai-exposed MDM-MCSF. PCR analysis of the LTR RU5 region showed that X4 HIV-1Lai entered into both types of macrophages in the same manner as R5 HIV-1 BaL. However, in contrast to MDM-5d, there was a block of HIV-1 Lai retrotransciption in MDM-MCSF. Cytokine profile analysis of the two types of macrophages showed that TNF-alpha, IL-6 and RANTES levels were higher in MDM-5d than in MDM-MSCF, while the IL10 level was higher in MDM-MCSF, both producing similar IL16 levels. Altogether, these data indicate that HIV-1 X4 strains enter into macrophages but that their replication is blocked thereafter in a different manner according to the activation status of the cells.
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PMID:The susceptibility of macrophages to human immunodeficiency virus type 1 X4 isolates depends on their activation state. 1123 83

Evidence suggests that feline immunodeficiency virus (FIV), causes pulmonary immunodeficiency. The overall objective of this study was to explore FIV-induced alterations in cell counts and cytokine gene expression in the pulmonary compartment during the acute stage infection. Bronchoalveolar lavage (BAL) cells were collected from FIV-infected and control cats at 0, 4, 10, and 16 weeks post-FIV infection for phenotype and cytokine analysis. The major change in BAL cellular populations following FIV-infection was the development of a neutrophilia. Total BAL cell counts and relative numbers of alveolar macrophages (AM), eosinophils, and lymphocytes remained similar in both groups. The RT-qcPCR analyses of AM purified from BAL showed constitutive expression of TNFalpha, IL6 and IL10 mRNAs that peaked during the acute stage of infection then declined. The TNFalpha and IL6 bioactive protein secretion showed a similar response. In contrast, IFNgamma expression increased progressively with time after infection and paralleled a progressive increase in FIV-gag mRNA in AM. The IL12 p40 expression also differed from the other cytokines in that there was a progressive decrease in the number of cats with AM IL12 expression following FIV infection. Infection of AM in vitro with FIV also caused an increase in TNFalpha and IL6 mRNA and bioactive protein suggesting that the increased cytokine response by AM following infection of cats with FIV is an intrinsic characteristic of FIV-infected AM. In summary, pulmonary immune changes seen in FIV-infected cats are similar to those seen in HIV-infected human patients.
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PMID:Constitutive expression of types 1 and 2 cytokines by alveolar macrophages from feline immunodeficiency virus-infected cats. 1135 52

Variable immune responses to hepatitis B virus (HBV) infection and recombinant HBV vaccines have been associated with polymorphisms in several genes within the human leukocyte antigen (HLA) complex. Analyses of polymerase chain reaction (PCR)-based genotyping data from 164 North American adolescents vaccinated with recombinant HBV products confirmed that HLA-DRB1*07 (relative odds [RO] = 5.18, P <.0001) and human immunodeficiency virus type 1 (HIV-1) infection (RO = 3.91, P <.001) were both associated with nonresponse to full-dose vaccination. Further associations were observed with single nucleotide polymorphisms (SNPs) at the IL2 and IL4 loci along with insertion/deletion variants at the IL12B locus (P =.003-.01). Host genetic associations were independent of one another as well as other HLA (A, B, C, and DQB1) and cytokine gene (IL4R, IL6, IL10, and TNF) variants. Statistical adjustments for nongenetic factors (gender, ethnicity, age, HIV-1 infection, and vaccination protocols) did not substantially alter the strengths of the genetic relationships. The overall distribution pattern of genetic variations was similar between the analyzed vaccinees and additional adolescents (n = 292) from the same cohort. In conclusion, DRB1*07 (or a closely linked allele) and immunoregulatory cytokine gene polymorphisms correlate with variable immune response to recombinant HBV vaccines.
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PMID:HLA and cytokine gene polymorphisms are independently associated with responses to hepatitis B vaccination. 1505 2

Antigen presentation and immune activation are essential to the effective control of infectious diseases. In 485 North American adolescents at high risk for genital Chlamydia trachomatis infection, we found 2 human leukocyte antigen variants (DRB1*03-DQB1*04 and DQB1*06) to be associated with recurrent Chlamydia infection (adjusted relative odds [RO], >2.0; P<.01, for both variants). A G-C-C haplotype corresponding to variants at IL10 (encoding interleukin-10 [IL-10]) promoter positions -1082, -819, and -592 was underrepresented in individuals with recurrent infection (RO, 0.59; P=.046). These genetic associations were independent of nongenetic factors, including number of sex partners, race, sex, duration of follow-up, and human immunodeficiency virus type 1 seropositivity. Consistent with the observed IL10 association, cervical secretions in female adolescents without the IL10 G-C-C haplotype had elevated IL-10 concentrations after Chlamydia infection, which may reflect involvement of a Chlamydia-specific mechanism for genetically mediated, differential IL-10 expression in the genital tract.
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PMID:Human leukocyte antigen and cytokine gene variants as predictors of recurrent Chlamydia trachomatis infection in high-risk adolescents. 1574 44

Chronic psychological stress has been suggested to play a role in disorders in which the immune system unexpectedly fails to respond in a protective manner. Chronic combined acoustic and restraint stress compromises the anti-bacterial defense mechanisms of female BALB/c mice. The immunodeficiency is characterized by an apoptotic loss of lymphocytes, reduced ex vivo-inducibility of TNF but increased inducibility of IL10, reduced T-cell proliferation, and impaired phagocyte functions. Stressed mice develop depression-like behavior that was monitored by a stress severity score (SSS). Besides a strain (BALB/c>CBA) and gender (male>female) dependent susceptibility to chronic stress, inbred mice have an individual coping ability. Importantly, the individual SSS strongly correlates with Escherichia coli dissemination after infection as well as with IL10-inducibility and circulating corticosterone levels of each animal.
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PMID:Stress susceptibility predicts the severity of immune depression and the failure to combat bacterial infections in chronically stressed mice. 1633 Jan 79

We investigated whether polymorphisms in genes associated with HIV disease progression and/or immune activation affect CD4+ T-cell recovery in HIV patients who began combination antiretroviral therapy (ART) with advanced immunodeficiency and achieved stable control of plasma viremia. Patients with CD4 T-cell counts <300 cells/microL (n = 33) and >400 cells/microL (n = 37) on ART were compared. A multiple case-control logistic regression associated carriage of BAT1(1,2) or interleukin (IL)6-174(2,2) with low CD4 T-cell counts (P = 0.012). BAT1*2 uniquely marks the central major histocompatibility complex region of a conserved haplotype (HLA-A1,B8,BAT1*2,TNFA-308*2,DR3,DQ2). There was no association between alleles carried at CCR5Delta32, CCR5 59029, CCR5 59353, CCR2+190 (V64I), SDF1 3'UTR, IL1A+4845, IL1B+3953, IL4-589, IL10-592, IL10-R1+536, IL10-R1+1112, IL12B 3'UTR, TNFA-308, or TNFA-1031 and CD4 T-cell counts. We suggest that immune activation and/or CD4 T-cell apoptosis in HIV patients on effective ART is influenced by genetic factors.
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PMID:Recovery of CD4+ T Cells in HIV patients with a stable virologic response to antiretroviral therapy is associated with polymorphisms of interleukin-6 and central major histocompatibility complex genes. 1634 Apr 66

Adaptive immune responses by dendritic cells (DCs) are critically controlled by Toll-like receptor (TLR) function. Little is known about modulation of TLR-specific signaling by other pathogen receptors. Here, we have identified a molecular signaling pathway induced by the C-type lectin DC-SIGN that modulates TLR signaling at the level of the transcription factor NF-kappaB. We demonstrated that pathogens trigger DC-SIGN on human DCs to activate the serine and threonine kinase Raf-1, which subsequently leads to acetylation of the NF-kappaB subunit p65, but only after TLR-induced activation of NF-kappaB. Acetylation of p65 both prolonged and increased IL10 transcription to enhance anti-inflammatory cytokine responses. We demonstrated that different pathogens such as Mycobacterium tuberculosis, M. leprae, Candida albicans, measles virus, and human immunodeficiency virus-1 interacted with DC-SIGN to activate the Raf-1-acetylation-dependent signaling pathway to modulate signaling by different TLRs. Thus, this pathway is involved in regulation of adaptive immunity by DCs to bacterial, fungal, and viral pathogens.
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PMID:C-type lectin DC-SIGN modulates Toll-like receptor signaling via Raf-1 kinase-dependent acetylation of transcription factor NF-kappaB. 1746 20


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