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)

Mononuclear phagocytes can be infected with the human immunodeficiency virus type 1 (HIV-1). Although these cells express CD4 antigen, which is the recognized cellular receptor for HIV, additional cell surface proteins such as the Fc receptor, might serve as receptors for infection. In order to study this possibility we used the U937 monocytic cell line as a target for HIV infection. Flow cytometry of U937 showed that 97% of cells expressed CD4, 33% expressed the high affinity 72 kD Fc receptor (FcRI), and 74% expressed the low-affinity 40 kD Fc receptor (FcRII). Virus neutralization tests were performed by preincubating heat-inactivated human anti-HIV sera with HIV-1, IIIB strain, and then challenging U937. After 13 days in culture, productive HIV-1 infection was monitored by reverse transcriptase activity. High concentrations of certain sera (10(-1)-10(-3) dilutions) neutralized HIV-1, but at subneutralizing concentrations (10(-4)-10(-6) dilutions), five of these sera enhanced viral infection approximately two- to threefold. This enhancement of HIV-1 infection was totally blocked by 1 microgram/ml recombinant soluble CD4 (rCD4) or by 0.5 microgram/ml anti-CD4 Leu3a monoclonal antibody. These results suggest that serum enhancement of HIV-1 infection, thought to be due to binding to the monocyte Fc receptor, requires HIV-1 binding to CD4, since rCD4 or Leu3a blocked this phenomenon.
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PMID:Inhibition of serum-enhanced HIV-1 infection of U937 monocytoid cells by recombinant soluble CD4 and anti-CD4 monoclonal antibody. 236 Oct 75

Low concentrations of serum obtained from a patient with acquired immunodeficiency syndrome (AIDS) enhanced the replication of human immunodeficiency virus type 1 (HIV-1) in a particular subclone of the CD-4-positive monocytoid cell line U937 clone 2. Cells of this subclone have a high expression of Fc receptors and a considerable degree of Fc-mediated phagocytic activity. IgG purified from the serum was also able to enhance the replication. These results indicate that low concentrations of human anti-HIV antibody may enhance HIV replication on human monocyte-macrophages. Furthermore, two mouse IgG1 monoclonal antibodies against gp120, the envelope glycoprotein of HIV-1, also induced enhancement at low concentrations. The binding of radiolabelled gp120 to the cells was increased at the same low concentrations. Antibodies against envelope glycoproteins may cause enhancement of HIV infection. Both normal and enhanced replication of HIV were completely inhibited by the masking of the binding site of CD4 molecules with F(ab')2 fragments of anti-CD4 antibody. Moreover, CD4-positive, Fc gamma RI-negative K562 cells and mouse macrophages failed to show any infection in the presence of antibody. These results suggest that CD4 molecules on the cell surface are necessary to cause enhancement of infection of HIV on monocyte-macrophages.
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PMID:Enhancement of human immunodeficiency virus (HIV) replication in human monocytes by low titres of anti-HIV antibodies in vitro. 255 88

Corticosteroids are used in treatment of a variety of human immunodeficiency virus (HIV)-related disorders. Preliminary reports of a temporal relationship between administration of these drugs to viral carriers and development of AIDS raised the possibility that they can modify the course of HIV infection. Because glucocorticoids can alter specific gene expression in at least one immunosuppressive murine retrovirus, mammary tumor virus, we explored the ability of dexamethasone (DXM) to upregulate chronic HIV replication or to alter transcription at the HIV-1 long terminal repeat (LTR). A clone of promonocytic cells chronically infected with HIV-1 could be converted to a productive state of replication by phorbol ester or halogenated pyrimidine exposure, yet was unperturbed by DXM used over broad concentrations (10(-4) to 10(-9) mol/L) and time intervals (24 to 96 hours). This unresponsiveness corresponded to the lack of a positive effect of DXM on HIV associated trans-activation in both monocytic and CD4+ T cells. These cells possessed the appropriate steroid receptors, as DXM downregulated Fc gamma type-I receptors in both normal and HIV-infected promonocytic cells. In addition, DXM could block the transcriptional enhancement of an HIV-LTR-linked reporter gene by phorbol ester, while leaving basal levels of HIV-LTR-directed transcription unperturbed. These data are discussed in the context of clinical reviews of short-term steroid use in HIV-infected individuals.
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PMID:Effect of glucocorticoids on chronic human immunodeficiency virus (HIV) infection and HIV promoter-mediated transcription. 275 16

Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.
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PMID:The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. 278 47

Human and murine mononuclear phagocytes express a high-affinity receptor for immunoglobulin G that plays a central role in macrophage antibody-dependent cellular cytotoxicity and clearance of immune complexes. The receptor (FcRI) may also be involved in CD4-independent infection of human macrophages by human immunodeficiency virus. This report describes the isolation of cDNA clones encoding the human FcRI by a ligand-mediated selection technique. Expression of the cDNAs in COS cells gave rise to immunoglobulin G binding of the expected affinity and subtype specificity. RNA blot analysis revealed expression of a 1.7-kilobase transcript in macrophages and in cells of the promonocytic cell line U937 induced with interferon-gamma. The extracellular region of FcRI consists of three immunoglobulin-like domains, two of which share homology with low-affinity receptor domains.
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PMID:Isolation and expression of functional high-affinity Fc receptor complementary DNAs. 291 49

Recent studies of cartilage-hair hypoplasia (CHH), a form of short-limbed dwarfism, have shown that all affected individuals have a cellular proliferation defect that results in a cellular immunodeficiency. However, only a minority of CHH individuals suffer from severe, life-threatening infections. For this reason, relevant immune defense mechanisms that may be responsible for maintaining intact host defenses in the majority of CHH individuals were studied. Spontaneous and allogeneic culture-induced (mixed lymphocyte response-MLR) specific and nonspecific (NK-like) cytotoxic mechanisms were analyzed and correlated with lymphocyte subpopulations present in CHH and normal individuals. Spontaneous natural-killer (NK) activity was present at or above normal levels, but culture-induced specific cytotoxicity and NK-like cytotoxicity as well as NK-like activity by T cell lines were significantly reduced in CHH individuals. The generation of radiation-resistant cytotoxicity, which normally occurs during allogeneic MLR, was markedly diminished in CHH, and was correlated with the decreased proliferation observed in CHH cultures. Preservation of spontaneous NK activity and loss of all forms of culture-induced cytotoxicity was associated with an increase in the proportion of lymphocytes bearing a thymic independent NK phenotype (OKM1+ OKT3- Fc gamma + low-affinity E+), and a significant decrease in thymic derived OKT3+ cytolytic T cell sub-populations in CHH individuals. Therefore, an intact cellular cytotoxic effector mechanism has been identified in CHH (i.e., NK activity). Natural cytotoxicity may be of importance in maintaining host resistance to viral infections despite diminished thymic-derived effector mechanisms in cartilage-hair hypoplasia.
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PMID:Impaired culture generated cytotoxicity with preservation of spontaneous natural killer-cell activity in cartilage-hair hypoplasia. 622 49

Antipeptide sera raised against the gp120/gp41 sequences of human immunodeficiency virus type 1 (HIV-1) were used to determine their capacity to enhance infection. Antisera to the five variable regions (V1 to V5) of gp120 and conserved parts of gp120 and gp41 facilitated infection of primary human macrophages with the homologous virus HIV-1 SF2mc. In contrast, heterologous virus infection with HTLV-IIIB was mediated only by antisera to the conserved regions, predominantly C4 and C5. Heterologous virus infection occurred more rapidly and was consistent between different cell donors. The neutralizing monoclonal antibody (MAb) SC258 (murine IgG2a) but not MAb 684-238 (mIgG1) against conformational epitopes of the V2 region also induced antibody-dependent infection enhancement (ADE). Therefore, preincubation with certain antibodies can cause altered tropism of the lymphocytotropic viruses mentioned above. Viral infection was completely abolished by preincubation with the F(ab)2 fragment of MAb 3G8 against the Fc gamma receptor III (CD16). A MAb (7.3F11) against the gp120-binding site of CD4 had no effect on viral infectivity. Possible mechanisms and their implications for disease progression are discussed.
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PMID:Lymphocytotropic strains of HIV type 1 when complexed with enhancing antibodies can infect macrophages via Fc gamma RIII, independently of CD4. 754 Mar 99

Human immunodeficiency virus (HIV) is commonly transmitted, during homosexual and heterosexual intercourse, through the rectal and cervicovaginal mucosa, foreskin and urethral epithelia. However, there is uncertainty about HIV transmission through the oral mucosa by oral sex. We have carried out a comparative immunohistological investigation of primate oral, cervicovaginal, foreskin, urethral and rectal epithelia for potential HIV receptors. We investigated epithelial tissues for CD4 glycoprotein, which is the principal receptor for HIV, Fc receptors of IgG for binding HIV-IgG antibody complexes, and HLA class II, which might enable HIV-bound CD4+ cells to gain access to the epithelial cells. CD4 glycoprotein was not found in oral, foreskin, urethral, vaginal or rectal epithelial cells, although CD4+ mononuclear cells were present in the lamina propria of each epithelium. Fc gamma II and Fc gamma III receptors were found in urethral, endocervical and rectal epithelia, and Fc gamma III and Fc gamma I receptors in the foreskin. However, Fc gamma receptors were not found in oral epithelium (buccal, labial, lingual or palatal) and only Fc gamma III receptors were detected in the gingival epithelial cells. HLA class II antigen was also not detected in foreskin, oral or rectal epithelium, but it was expressed by endocervical cells from most human specimens and in male urethral epithelia of non-human male primates. Langerhans' cells were found in all epithelia except those of the urethra and rectum, and they can express CD4 glycoprotein, Fc gamma receptors and HLA class II antigen. The mean number of Langerhans' cells expressing CD4 in the upper third of oral epithelium was significantly lower compared with vaginal epithelium or foreskin. The HIV-binding V1 domain of CD4 was significantly decreased in Langerhans' cells present in oral compared with vaginal epithelium. The results suggest that the foreskin in uncircumcised men and the cervicovaginal epithelium in females might become infected via the CD4+ Langerhans' cells. However, urethral infection might be mediated by HIV-antibody complexes binding to urethral epithelial Fc gamma receptors. The paucity of Langerhans' cells expressing the V1 domain of CD4, the absence of Fc gamma receptors, and a lack of expression of HLA class II antigens in most oral epithelial cells, argue against transmission of HIV through the normal intact oral mucosa.
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PMID:Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia. 755 38

The aim of this study was to assess the cytolytic potential of natural killer (NK) cells from human immunodeficiency virus type 1 (HIV-1)-infected patients, at different stages of the disease. Twenty HIV-1 seronegative donors as well as sixty HIV-1 seropositive patients were studied. Phytohemagglutinin and/or the anti-CD16 monoclonal antibody Kd1 were used to redirect the peripheral blood lymphocyte lysis of these patients to the 51Cr-labeled Fc gamma receptor-positive P815 murine mastocytoma target cell line. In parallel, NK cytotoxicity to tumor targets was investigated. Seronegative as well as HIV-1 Center for Disease Control (CDC) stage II patients showed maintained cytolytic activity. The cytolytic potential declined with disease progression, starting with CDC IVC2 patients, and was strongly diminished in acquired immunodeficiency syndrome stage patients. This defect was accompanied by decreased cytolytic activity to tumor targets and was not corrected by the in vitro addition of interleukin-2. The number of cells bearing a mature NK phenotype was normal in all the study groups. Our data suggest that the impaired NK cytotoxicity to tumor targets described during the progression of HIV-1 disease may be related to the progressive loss of function of surface receptors involved in NK cell triggering.
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PMID:Analysis of the cytolytic activity mediated by natural killer cells from acquired immunodeficiency syndrome patients in response to phytohemagglutinin or anti-CD16 monoclonal antibody. 805 46

A patient with refractory human immunodeficiency virus (HIV)-related immune thrombocytopenic purpura (ITP) was treated with 3G8 (anti-CD16) monoclonal antibody on days 1, 3, and 8 (25, 25, and 50 mg were administered intravenously, respectively). Side effects were those expected after the administration of a xenogenic protein, but a severe bone pain occurred from the second injection. At the time of the initiation of the treatment the platelet count was 20,000/mm3 and the absolute CD4 number was 100/mm3. We obtained a long-term correction of thrombocytopenia and, to a lesser extent, there was a stabilization of CD4 lymphocytes for 18 months. We observed a significant stimulation of natural killer (NK) function and an elevation in the serum level of tumor necrosis factor alpha, interferon gamma, and granulocyte-macrophage colony-stimulating factor. This suggests that in HIV-related ITP the removal of platelets is mediated by low-affinity Fc gamma receptors (CD16). The stimulation of NK function and elevation in CD4+ lymphocytes may be related to the production of cytokines by activated human NK cells through the interaction of their CD16-bearing receptor with the 3G8 monoclonal antibody. This observation warrants confirmation and further clinical trials.
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PMID:Biologic response to anti-CD16 monoclonal antibody therapy in a human immunodeficiency virus-related immune thrombocytopenic purpura patient. 809 46


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