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)

The env gene of human immunodeficiency virus type 1 (HIV-1) encodes gp 120/41 which plays an important role in the viral infection process and pathogenesis. The surface glycoprotein gp120 is a candidate molecule for the development of a subunit vaccine against HIV-1-induced acquired immunodeficiency syndrome (AIDS). However, thorough studies on the immunobiology of this molecule are hampered by the lack of a suitable model. With this background in mind, and in order to learn more on anti-gp120 cellular immunity, we attempted to develop gp120-expressing human cell clones. Thus by transfecting a human lymphoid cell line of B lineage (Raji), which is known to be resistant to the natural killer cell activity, with an expression vector encoding the envelope and vpu, we established three clones that stably express gp120/41 and vpu. The surface glycoprotein gp 120 is also expressed on the cell surface of these clones. The transfected cells from syncytia with CD4+ human cell lines as well as with peripheral blood mononuclear cells (PBMC) leading to the death of the fused cells. This observation represents additional evidence for the eventual depletion of CD4+ viral targets that fuse with adjacent HIV-infected, gp 120-expressing cells. The latent Epstein-Barr virus genome present in the transfected cells, was not induced to express the lytic cycle antigens. The densities of the surface expression of a number of molecules examined remained unchanged in the transfected cells except for the surface IgM, which increased significantly (P < 0.05) in two clones. One of the clones exhibited a significantly (P < 0.05) reduced proliferation rate as compared to the other clones. The transfected cells of all the three clones showed a significantly (P < 0.01) increased susceptibility to lysis by the PBMC from normal, healthy individuals in a 16-hr 51Cr-release assay. This is the first report of the MHC- and antibody-independent lysis of human cells transfected with the HIV-1 surface glycoprotein. The transfected cells also served as targets in a gp120-specific antibody-dependent cellular cytotoxicity assay. We anticipate that the present model will prove very useful for studying the gp120-specific immune responses in HIV-infected individuals.
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PMID:Stable expression of the transfected HIV-1 env gene in a human B cell line: characterization of gp120-expressing clones and immunobiological studies. 842 93

Class II-deficient combined immunodeficiency (CID) is a hereditary disease resulting in abrogation of transcription of the class II genes of the major histocompatibility complex, due to a defect in a trans-acting regulatory factor. Cell lines from certain CID patients lack factor binding at multiple sites in class II promoters in vivo. A mutation in one of the promoter binding proteins could explain this 'bare' phenotype only if these factors bind cooperatively or in a temporal hierarchy. Alternatively, the mutation could affect the configuration of the promoter within the MHC locus. Here, we provide evidence that the factor(s) defective in class II-deficient CID controls the accessibility of class II promoters within the environment of the MHC. The in vivo occupancy of wild type and mutated class II promoter constructs was examined in stable transfectants of normal and CID-derived cell lines. The CID promoter phenotype could not be reproduced in a normal cell line by eliminating binding at any one promoter element, suggesting that these factors bind independently, both spatially and temporally. In contrast, promoter occupancy was partially restored in two CID lines at a randomly integrated wild type promoter, implying that the promoter is inaccessible to factors in its native environment, but accessible when moved to another location in the genome.
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PMID:Promoter accessibility within the environment of the MHC is affected in class II-deficient combined immunodeficiency. 842 78

Sensory and sympathetic ganglia from 12 cases of human immunodeficiency virus type 1 (HIV-1) infection, all but one without clinical evidence of peripheral nerve disease, were studied immunocytochemically for their content of lymphocytes, macrophages, MHC Class II antigens and HIV-1 and cytomegalovirus antigens. They were compared with ganglia from 7 normal and peripheral nerve disease control cases. Compared with normal controls, many of the ganglia from the majority of HIV-1-infected subjects contained more T lymphocytes and macrophages and enhanced MHC class II expression. A few also showed occasional neuronal degeneration which was not present in the normal controls. In 7 cases HIV-1 gp41 envelope protein and/or p24 core protein antigens were detected in intraganglionic macrophages. Sensory ganglia contained more gp41 HIV-1 antigen than sympathetic ganglia. There was no clear correlation between detection of HIV-1 antigens in ganglia and in the CNS. Detection of HIV-1 antigens in ganglia was more common in cases of HIV-1 infection that had progressed to clinical AIDS by the time of death (71%) than in those that had not done so (40%). It is concluded that there is commonly a mild ganglionitis which is asymptomatic in the absence of detailed clinical testing and frequently associated with local presence of HIV-1 antigens in sensory and sympathetic ganglia in AIDS.
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PMID:Sensory and sympathetic ganglia in HIV-1 infection: immunocytochemical demonstration of HIV-1 viral antigens, increased MHC class II antigen expression and mild reactive inflammation. 844 99

Coinfections of human immunodeficiency virus (HIV), EBV, and HTLV or sperm proteins act synergistically to enhance infectivity and replication and expand cellular tropism. While some aspects of these synergisms are understood, others are not. We have found that membrane or surface proteins of CMV, HTLV, EBV and sperm proteins share large regions of similarity with the CD4 protein of T-helper lymphocytes. Since HIV uses CD4 as a receptor, it may bind to CD4 homologues on CMV, HTLV, EBV or sperm proteins. HIV could then "piggyback" with these viruses into cells with which it normally has no tropism. Similarly, HIV may expand the cellular tropism of CMV, or EBV. Such a piggyback mechanism may provide insight into the formation or presentation of CD4-like antigens from CMV, HTLV, EBV and sperm proteins with class II MHC-like antigens on HIV (gp160 and Nef proteins) and may break immunological tolerance, inducing the autoimmunity observed against both CD4+ and class II MHC+ T cells in AIDS patients.
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PMID:Does HIV "piggyback" on CD4-like surface proteins of sperm, viruses, and bacteria? Implications for co-transmission, cellular tropism and the induction of autoimmunity in AIDS. 847 53

Definition of the immunological mechanisms involved in protective immunity against lentiviral infections is crucial to the development of an effective vaccine. The induction of gag- and env-specific cell-mediated immune responses was studied in cats following vaccination with whole inactivated feline immunodeficiency virus (FIV). Cats were immunized by inoculation with three doses of paraformaldehyde-inactivated FIV, derived from the feline lymphoid cell line, FL-4, which is persistently infected with the Petaluma isolate of FIV. Autologous or allogeneic skin fibroblasts either infected with recombinant FIV gag- or env-vaccinia virus or pulsed with FIV env peptides were used as targets in chromium-51 release assays. Effector cells were fresh peripheral blood mononuclear cells. Following the third immunization, all vaccinated cats, but none of the control cats immunized with adjuvant alone, had detectable FIV env-specific lymphocytotoxicity in their peripheral blood. Two cats also exhibited gag-specific activity. There was no recognition of either allogeneic skin fibroblasts infected with recombinant vaccinia virus or autologous target cells infected with wild-type vaccinia virus, indicating the specificity and MHC-restricted nature of the response. Vaccinated cats, but not control cats, were protected from challenge with the homologous Petaluma isolate of FIV. Partial epitope mapping of the env-specific cytotoxic response was performed using overlapping 10-amino acid peptides from the env V3 domain of FIV. This response appeared to be directed at env peptide 1 (RAISSWKQRN) and env peptide 3 (QRNRWEWRPD), which lie adjacent to a beta-turn within the V3 domain.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of gag- and env-specific cytotoxic T lymphocytes in protective immunity to feline immunodeficiency virus. 855 8

The core polyprotein of feline immunodeficiency virus (FIV) was expressed in primary feline T-lymphocytes using a retroviral vector. These cells were used as antigen-presenting stimulator cells (APSC) for the in vitro induction of cytotoxic T-lymphocytes (CTL) from feline peripheral blood mononuclear cells (PBMC). CTL from 4 cats chronically infected with the Petaluma strain of FIV specifically lysed autologous FIV-infected targets in an MHC-restricted manner. The CD8 phenotype of more than 70% of the induced effector cells (97% for cells from one cat) was consistent with MHC class I-restricted cytotoxicity. In addition, it was possible to detect low levels of core polyprotein-specific lysis from effector cells of two of the FIV-infected cats. When observed, the level of lysis, measured as a percentage of specific 111In release, was lower for the transgenic gag-expressing targets than for FIV-infected targets. The difference in killing may reflect the low level of core CTL were not detected in either PBMC stimulated with cells transduced by a retroviral vector without the FIV gag sequence or PBMC from an uninfected cat stimulated with autologous transgenic APSC. The detection of FIV-specific CTL from infected cats following stimulation with transgenic APSC suggests a role for retroviral vectors in determining CTL specific for individual lentiviral proteins in protective immunity.
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PMID:Retroviral vector-transduced cells expressing the core polyprotein induce feline immunodeficiency virus-specific cytotoxic T-lymphocytes from infected cats. 857 69

The Xid immunodeficiency was characterized by a total lack of B1 cells and reduced numbers and functions of B2 cells. In BALB.Xid mice, this defect results in an reduced susceptibility against infections with parasites such as Trypanosoma cruzi and Leishmania major. Since IL-7 acts on the B cell compartment by stimulation of pre-B cell proliferation, we analyzed the effect of recombinant IL-7 on L. major infection in BALB.Xid mice. After application of a single dose of IL-7 simultaneously with the infection, the clinical course in BALB.Xid mice was markedly aggravated, resembling that of normal BALB/c mice. IL-7-induced disease promotion was accompanied by an up to 100-fold higher parasite load in several tissues of these mice. When cytokine production of purified, L. major-specific CD4+ T cells from lesion-draining lymph nodes was examined, the IFN-gamma production seen in untreated BALB.Xid mice was suppressed in IL-7-treated animals. One of the major effects of IL-7 treatment in the lymphoid organs of BALB.Xid mice was the increase of the total number of B220, sIgM and MHC II-positive cells. These cells belonged to the B2 subset, since cells expressing surface molecules characteristic for B1 cells (Mac-1 and Ly-1) remained absent in spleens, lymph nodes and the peritoneum. In conclusion, selective up-regulation of B2 cells by IL-7 in the absence of B1 cells is associated with disease aggravation in L. major-infected BALB.Xid mice.
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PMID:Effect of IL-7 treatment on Leishmania major-infected BALB.Xid mice: enhanced lymphopoiesis with sustained lack of B1 cells and clinical aggravation of disease. 858 86

Peripheral blood lymphocytes expressing CD8 and CD57 determinants are a small (1-15%) subset in healthy humans. CD8+, CD57+ peripheral blood lymphocytes may be divided by the level of CD8 expression, into CD8+high (CD57+) T-cells and CD8+low (CD57+) natural killer (NK) cells. CD8+high (CD57+) T-cell numbers are increased in human cytomegalovirus (HCMV)-seropositive subjects, and there is substantial evidence that HCMV is integral in the development of this subset in health and disease. Furthermore, the CD8+high (CD57+) subset is clonally derived, expressing a limited range of T-cell receptors, and are therefore likely to have restricted antigen specificity. Functionally, CD8+low(CD57+) cells exhibit NK activity, while CD8+high(CD57+) T-cells from healthy subjects mediate contact-dependent suppression in several in vitro systems including: (i) pokeweed mitogen-induced proliferation and immunoglobulin synthesis, and (ii) generation of antiviral MHC-restricted cytotoxic T-lymphocytes. This is distinct from the nonspecific, soluble factor-mediated suppression exhibited from a phenotypically similar subset in human immunodeficiency virus (HIV) and bone marrow transplant recipients. This suggests an important immunoregulatory, suppressive role for CD8+high(CD57+) T-cells that may be potentiated by HCMV and altered in diseases associated with higher numbers of this subset including HIV, allograft recipients and rheumatoid arthritis.
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PMID:The role of CD8+, CD57+ cells in human cytomegalovirus and other viral infections. 866 46

Precise regulation of major histocompatibility complex class II (MHC-II) gene expression plays a crucial role in the control of the immune response. A major breakthrough in the elucidation of the molecular mechanisms involved in MHC-II regulation has recently come from the study of patients that suffer from a primary immunodeficiency resulting from regulatory defects in MHC-II expression. A genetic complementation cloning approach has led to the isolation of CIITA and RFX5, two essential MHC-II gene transactivators. CIITA and RFX5 are mutated in these patients, and the wild-type genes are capable of correcting their defect in MHC-II expression. The identification of these regulatory factors has furthered our understanding of the molecular mechanisms that regulate MHC-II genes. CIITA was found to be a non-DNA binding transactivator that functions as a molecular switch controlling both constitutive and inducible MHC-II expression. The finding that RFX5 is a subunit of the nuclear RFX-complex has confirmed that a deficiency in the binding of this complex is indeed the molecular basis for MHC-II deficiency in the majority of patients. Furthermore, the study of RFX has demonstrated that MHC-II promoter activity is dependent on the binding of higher-order complexes that are formed by highly specific cooperative binding interactions between certain MHC-II promoter-binding proteins. Two of these proteins belong to families of which the other members, although capable of binding to the same DNA motifs, are probably not directly involved in the control of MHC-II expression. Finally, the facts that CIITA and RFX5 are both essential and highly specific for MHC-II genes make possible novel strategies designed to achieve immunomodulation via transcriptional intervention.
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PMID:Regulation of MHC class II genes: lessons from a disease. 871 17

Studies on Nef, a regulatory protein encoded by human immunodeficiency virus (HIV), suggest it plays an important role in HIV pathogenesis. Previously, we reported that Nef binds to class II MHC antigens and induces proliferation of human peripheral blood mononuclear cells (PBMC). Herein, we further characterize PBMC responses to Nef. Polyclonal antisera generated against Nef synthetic peptides blocked proliferation. Responses were T cell-specific and required antigen-presenting cells (APC). T cells responded in the presence of paraformaldehyde-inactivated APC, suggesting that Nef is presented in an unprocessed form. Nef-stimulated cells produced IL 2 and IFN gamma, products of T helper-1 cells. Thus, Nef has superantigen properties in that it binds to MHC class II antigens, does not need processing to be presented by APC, and activates T cells, causing proliferation and production of the T helper 1 cytokines, IL 2 and IFN gamma. The identification of an HIV protein that activates T cells is of considerable interest, given that HIV replicates in T cell blasts but not in quiescent cells.
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PMID:Characterization of Nef-induced CD4 T cell proliferation. 876 94


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