Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Neuropathological studies have shown that human immunodeficiency virus type 1-infected cells within the brain express several markers characteristic of macrophages and could either be microglial cells, or monocytes invading the CNS, or both. To better define the target cells of human immunodeficiency virus type 1 within the brain, we have studied human microglial cells, both in vivo and in vitro, and compared them to monocytes for their antigenic markers and their susceptibility to human immunodeficiency virus type 1 infection. Brain-derived macrophages were isolated from primary cortical and spinal cord cultures obtained from 8 to 12-week-old human embryos. The isolated cells presented esterase activity, phagocyted zymosan particles, expressed several (Fc receptors, and CD68/Ki-M7 and CD11b/CR3 receptors) of the macrophagic antigenic markers, and appeared to be resident microglial cells from human embryonic brain. Conversely, brain-derived macrophages did not express antigens CD4, CD14, or CD68/Ki-M6, which are easily detected on freshly isolated monocytes. Using these antigenic differences between isolated microglial cells and monocytes, we have observed that two populations of macrophages could be individualized. In the normal adult brain, microglial cells were numerous in both the gray and the white matter. The infrequent cells sharing antigens with monocytes were found almost exclusively around vessels. In 8 to 12-week-old human embryos, microglial cells were found in both the parenchyma and the germinative layer. Cells sharing antigens with monocytes were only found at the top of and inside the germinative layer. In brain tissue from patients with human immunodeficiency virus type 1 encephalitis, cells sharing antigens with monocytes are abundant not only around the vessels but also in the parenchyma. In double-labeling experiments, human immunodeficiency virus type 1-infected cells showed monocyte antigens. Finally, microglial cells also differ from monocytes in their in vitro susceptibility to human immunodeficiency virus type 1 infection; after stimulation by r-TNF alpha or GmCSF, monocytes but not microglial cells can replicate human immunodeficiency virus type 1. This in vitro difference in human immunodeficiency virus type 1 susceptibility between monocytes and microglial cells together with the presence of monocytic antigens within the brain tissue of human immunodeficiency virus type 1-infected patients suggest that human immunodeficiency virus type 1-infected cells within the brain are either monocytes that have crossed the blood-brain barrier and spread through the tissue or perivascular microglial cells that, after phagocyting infected blood lymphocytes, subsequently contain viral antigen and migrate to brain tissue.
...
PMID:Human microglial cells: characterization in cerebral tissue and in primary culture, and study of their susceptibility to HIV-1 infection. 170 49

Lymphocyte chemoattractant factor (LCF) is a tetrameric glycoprotein of 56,000 relative molecular mass produced by activated T lymphocytes. LCF binds to CD4 and has previously been found to stimulate migration of CD4+ lymphocytes and monocytes. Because human eosinophils, like T cells and monocytes, express CD4, we examined functional responses of eosinophils to LCF. Recombinant LCF (rLCF) expressed in COS cells was purified on a CD4 affinity column. Migration of eosinophils was elicited by rLCF at low concentrations: the 50% effective dose (ED50) was 10(-12) to 10(-11) M, concentrations 100- to 1,000-fold lower than the ED50s for the recognized eosinophil chemoattractants C5a and platelet-activating factor. Two other ligands which bound to CD4, human immunodeficiency virus-1 envelope glycoprotein gp120 and monoclonal antibody OKT4, also stimulated eosinophil migration. Monovalent OKT4 Fab competitively inhibited eosinophil responses to rLCF. rLCF did not influence other functional responses of eosinophils tested, including degranulation, superoxide generation, leukotriene C4 production, in vitro survival, or surface expression of the adherence receptor CR3 (CD11b), human histocompatibility leukocyte antigen DR, or interleukin 2 receptor p55 (CD25). We conclude that CD4 on eosinophils is capable of transducing a migratory stimulus and serves as a receptor for a chemoattractant lymphokine LCF. T cell-derived LCF may contribute to recruitment of eosinophils and CD4+ mononuclear cells concomitantly at inflammatory reactions.
...
PMID:CD4-mediated stimulation of human eosinophils: lymphocyte chemoattractant factor and other CD4-binding ligands elicit eosinophil migration. 185

The phenotype and functions of monocytes in patients with haemophilia A and age-matched controls were studied. Fourteen male haemophiliacs were classified in three categories according to the mean number of units of factor VIII received during the last 5 years. Eleven patients were positive for antibodies to human immunodeficiency virus but none of our patients were homosexuals or drug abusers, nor do they fulfill the criteria of acquired immunodeficiency syndrome. Patients treated with high amounts of factor VIII concentrates (greater than 3 x 10(5) U/year) showed a significantly lower percentage of monocytes expressing HLA-DR, LFA-1 and CR3 antigens as compared with patients receiving lower amounts of factor VIII (less than 2 x 10(6) U/year) or controls. Kinetics of DR, LFA-1 and CR3 in cultured monocytes showed tht they were lost faster by monocytes from haemophiliacs treated with large amounts of factor VIII than by control monocytes. Adherence ability and chemotactic response of monocytes from patients treated with less than 3 x 10(5) U/year of factor VIII were also impaired. Although phagocytic indices were in normal ranges in haemophiliacs, a significant difference was observed between percentages of phagocytic monocytes from haemophiliacs treated with the largest doses of factor VIII and normal controls. Tests for respiratory burst activity, measured by chemiluminescence and superoxide anion generation, and Staphylococcus aureus killing were in normal ranges in haemophiliacs' monocytes.
...
PMID:Phenotypic and functional abnormalities in monocytes from patients with haemophilia A treated with factor VIII concentrates. 282 91

The functional role of the LFA-1 molecule in the interaction between helper T lymphocytes and B lymphocytes was investigated using lymphocytes from patients with leukocyte adhesion deficiency, an inherited immunodeficiency characterized by a defective leukocyte expression of the LFA-1, Mac-1 (CR3) and p150,95 molecules. The ability of LFA-1- T lymphocytes to provide antigen-specific help for HLA-identical LFA-1+ B lymphocytes was reduced while their antigen-specific activation was normal. Antigen-independent conjugate formation between resting, nonactivated LFA-1- T lymphocytes and LFA-1+ B lymphocytes was impaired while LFA-1- B lymphocytes bound LFA-1+ T lymphocytes normally. Conjugate formation of activated LFA-1- T lymphocytes was mostly mediated by the CD2-LFA-3 adhesion pathway while the ICAM-1 molecule, a ligand of LFA-1, had no function. These results demonstrate that LFA-1 plays a major role in the cognate interaction between helper T lymphocytes and B lymphocytes that cannot be mediated instead by CD2 or other molecules on resting T lymphocytes.
...
PMID:The role of lymphocyte function-associated antigen 1 (LFA-1) in the adherence of T lymphocytes to B lymphocytes. 304 49

Microglia, the resident tissue macrophages of the central nervous system, have a highly differentiated morphology and do not express many of the antigens typically associated with other tissue macrophages. Activation of microglia is associated with a change in morphology and an increase in their repertoire of antigen expression. Microglia become activated in many neuropathological conditions including chronic neurodegenerative diseases and human immunodeficiency virus neuropathology, yet little is known of the mechanisms involved. Here we demonstrate for the first time that microglia can be activated and induced to divide and/or undergo apoptosis via a beta 2-integrin (complement receptor type 3, CR3, Mac-1 or CD11b/CD18) using an anti-CR3 monoclonal antibody (McAb5C6). This antibody, which has been shown to block myelomonocytic recruitment during central nervous system inflammation, is unique in that it can cross the intact blood-brain barrier to activate microglia. Since CR3 not only binds the iC3b component of the alternative complement cascade but also denatured proteins this suggests a potential route for microglia activation in neuropathological conditions.
...
PMID:Mitosis and apoptosis of microglia in vivo induced by an anti-CR3 antibody which crosses the blood-brain barrier. 825 20

Transcription of human immunodeficiency virus (HIV) type 1 and other viruses is regulated by the transcription factor NF-kappaB, which interacts with the multifunctional cellular protein p300. p300, originally identified by its ability to bind adenovirus early region 1A (E1A), has also been shown to regulate HIV transcription through its interaction with NF-kappaB. The 13S form of E1A activates HIV gene expression, while the 12S form represses its transcription. In this report, we have investigated whether these divergent effects of E1A are dependent upon common or distinct cellular cofactors, including p300, pRb, and the TATA box-binding protein (TBP). Unlike activation in the absence of E1A, cooperative stimulation of HIV gene expression by 13S E1A and RelA was independent of the ability of E1A to bind p300 but was critically dependent on the E1A CR3 region which associates with TBP. In contrast, inhibition of basal HIV gene expression by the 12S form of E1A was dependent on p300 but not pRb or TBP. Interestingly, mutation of the CR2 region of 12S E1A responsible for pRb binding abolished the repression of HIV transcription stimulated by tumor necrosis factor alpha, suggesting that repression of cytokine-activated transcription involves cofactors different from those used in unstimulated cells. Repression and activation of HIV transcription by different forms of E1A are mediated by distinct sets of cellular cofactors. These findings suggest that E1A has evolved to interact by alternative mechanisms with a transcriptional coactivator and its associated cofactors to differentially modulate cellular and viral gene expression.
...
PMID:Distinct domains of adenovirus E1A interact with specific cellular factors to differentially modulate human immunodeficiency virus transcription. 903 32

Several lines of evidence suggest a dysregulation of the complement system in human immunodeficiency virus-1 (HIV-1) infected patients. The aim of this study was to elucidate whether CD4+ alveolar lymphocytes from HIV-1 infected patients show a loss of complement regulatory proteins that would render these cells susceptible to antibody-dependent complement-mediated cytotoxicity. We investigated the expression of complement regulatory (CD46, CD55, CD59) and complement receptor (CR1, CR2, CR3, CR4) proteins on alveolar cells by flow cytometry. Cells were obtained by bronchoalveolar lavage from 17 HIV-1 infected and 12 HIV-1 negative individuals. Expression of adhesion molecules (leucocyte functional associated antigen-1 (LFA-1), intercellular adhesion molecule-1 (ICAM-1)) and CD30 were evaluated in patient subgroups. In addition, interleukin (IL)-1beta, tumour necrosis factor alpha (TNF-alpha), IL-4 and interferon gamma (IFN-gamma) concentrations were measured in supernatants of alveolar cells. We found a significantly reduced expression of CD46 and CD59 on CD4+ alveolar lymphocytes from HIV-1 infected individuals, whereas the expression of CR3, CR4, ICAM-1 and CD30 was increased. IL-1beta and TNF-alpha concentration in supernatants of alveolar cells was augmented in HIV-1 infected patients, but did not correlate with the expression of surface molecules. IFN-gamma concentration was also increased and showed an inverse relationship to the surface expression of CD30 on CD4+. Our data suggest that in human immunodeficiency virus-1 infection an increased level of activation is associated with a diminished expression of complement regulatory proteins on CD4+ alveolar lymphocytes. This phenomenon might contribute to the depletion of CD4+ lymphocytes and the local immunodeficiency in the pulmonary compartment.
...
PMID:Expression of complement receptors and regulatory proteins on alveolar CD4+ lymphocytes from human immunodeficiency virus-1 infected individuals. 927 12

We investigated the phagocytic function of monocytes in 7- to 10-year-old children horizontally infected with human immunodeficiency virus type 1 (HIV-1) in comparison to that in healthy sex- and age-matched controls. CR3-mediated phagocytosis was increased in patients with HIV-associated pulmonary tuberculosis, independently of CD4 counts and p24 antigenemia.
...
PMID:Phagocytic function of monocytes in children with human immunodeficiency virus type 1 infection. 1070 8

After the transition from the acute to the chronic phase of human immunodeficiency virus (HIV) infection, complement mediates long-term storage of virions in germinal centers (GC) of lymphoid tissue. The contribution of particular complement receptors (CRs) to virus trapping in GC was studied on tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2-C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells of an individual in the presymptomatic stage. Although they did so at a lower efficiency, these antibodies were able to remove HIV from tonsillar cells of patients under highly active antiretroviral therapy, suggesting that the C3d-CR2 interaction remains a primary entrapment mechanism in treated patients as well. In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus, targeting CR2 may facilitate new approaches toward a reduction of residual virus in GC.
...
PMID:Detachment of human immunodeficiency virus type 1 from germinal centers by blocking complement receptor type 2. 1093 8

HIV stimulates strong immune CD8(+) cytotoxic T lymphocytes (CTL) response in infected people, despite causing an immunodeficiency. It has been demonstrated that this response could be very important for the control of the virus. We have shown previously that a recombinant fowlpox virus (rFWPV), expressing the multi-epitope polypeptide (MEP) from HIV-1 TAB9, induces strong and protective Th1 and CTL responses in Balb/c mice. Here, we have studied the CTL response against MEPs TAB9 and CR3 after immunizing with rFWPVs, where these genes are under the control of a strong synthetic early/late promoter or the 7.5 kDa promoter from vaccinia virus. TAB9 expression was increased by more than 9-fold using the strong promoter, which was translated into a two times increase in CTL response. The overall expression of CR3 was already ten times higher when compared with TAB9 with the 7.5 kDa promoter, but the use of a stronger promoter showed no effect either on the expression or CTL response. Moreover, rFWPV expressing TAB9 induced a stronger CTL response than those expressing CR3, measured as the number of interferon- gamma -secreting splenocytes, in spite of its lower antigen expression levels. These results suggest that the capacity of a stronger promoter to increase the MEP expression and/or CTL response against their epitopes is highly dependent on the nature of the polypeptide used.
...
PMID:Effect of promoters on cellular immune response induced by recombinant fowlpox virus expressing multi-epitope polypeptides from HIV-1. 1245


1 2 Next >>

---