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

LP-BM5 murine leukemia virus (MuLV) induces an immunodeficiency syndrome (MAIDS) in C57BL/6 mice which resembles immunological abnormalities observed in early stages of human AIDS. In our study, MAIDS virus-infected mice were exposed to low doses of ultraviolet radiation (UVR) before and after virus inoculation and compared with MAIDS-infected but not UVR-exposed mice. In all tested parameters (blood IgM levels; mitogenic responses to PHA, ConA, LPS and anti-mu; MLR; antigenic response to SRBC; enlargement and histopathologic changes of the spleen) we observed the same trend: changes due to MAIDS infection were more pronounced in the UVR-exposed group than in the unexposed group. Statistically significant differences between these two groups were seen for mitogenic responses at two different time points after virus inoculation. These results demonstrate that in vivo UVR exposure enhances the immunosuppressive effects of a retroviral infection. UVR exposure may affect the progression of AIDS in a similar manner.
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PMID:In vivo exposure to ultraviolet radiation enhances pathogenic effects of murine leukemia virus, LP-BM5, in murine acquired immunodeficiency syndrome. 133 87

CD4+ T cell recognition of the simian immunodeficiency virus (SIV) surface envelope (env) glycoprotein was examined by using a panel of 10 T cell lines and 4 T cell clones derived from 10 individual macaques immunized with inactivated SIV or recombinant SIV env proteins. The results demonstrated that CD4+ T cells from each animal recognized between 1 and 7 peptides in 4 distinct regions of the protein including both variable and conserved domains. MLR of PBMC from selected macaques together with RFLP analysis by using the HLA DR beta probes suggested that animals of distinct MHC class II haplotypes can recognize identical peptides. These T cell epitopes within conserved regions of the envelope protein, together with identified linear B cell epitopes recognized by neutralizing antibodies, may be relevant in vaccine design.
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PMID:Heterogeneity in the recognition of the simian immunodeficiency virus envelope glycoprotein by CD4+ T cell clones from immunized macaques. 138 39

Recombinant sCD4-based proteins were evaluated for their effects on antigen-stimulated proliferation of human peripheral blood mononuclear cells (PBMC) and for antiviral activity against PBMC infected with human immunodeficiency virus (HIVD34). Two sCD4-based proteins were solubilized, refolded, and purified to homogeneity from recombinant E. coli and consisted of the 178 amino-terminal residues of CD4 fused with the translocating and catalytic domains of Pseudomonas exotoxin A (sCD4-PE40) or 183 amino-terminal residues of CD4 (sCD4-183); a third sCD4 consisting of 369 amino acids of CD4 was purified from recombinant mammalian cells for comparative purposes (sCD4-369). Increasing molar concentrations of these sCD4s were evaluated for inhibition of PBMC proliferation induced by alloantigen (MLR), by tetanus toxoid (TTOX), or in response to crosslinking with antibody to CD3 (OKT3). In addition, the concentrations of each protein required to inhibit replication of the HIVD34 isolate in primary PBMC was determined by quantitation of HIV p24 antigen released into supernatant fluids by infected cells. By comparing antiviral activity with anti-proliferative activity a relative estimate of the selectivity index for each recombinant sCD4 was determined. Proliferation of PBMC in response to alloantigen or OKT3 was less sensitive to inhibition than proliferation induced by TTOX, and the selectivity indices estimated for sCD4-PE40 were 170, 170 and 17, respectively. The selectivity index for sCD4-183 was greater than 350 under all assay conditions. Comparative evaluation of alloantigen-stimulated proliferation with antiviral activity of sCD4-183 versus sCD4-369 suggested that the E. coli-derived sCD4-183 may have a higher selectivity index under these conditions than its mammalian cell-derived counterpart.
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PMID:Effects of a soluble CD4 and CD4-Pseudomonas exotoxin A chimeric protein on human peripheral blood lymphocytes: lymphocyte activation and anti-HIV activity in vitro. 180 85

We report the outcome of a non-T-cell-depleted bone marrow transplant from an HLA partially incompatible, MLR-positive, parental donor in a patient with an unusual form of immunodeficiency characterized by a lack of CD8 T cells and a failure of the CD4 cells to display functional activity in vitro. Without conditioning, and following a mild and transient GVHD, donor T cells persist in trace amounts in the host, where they coexist with the nonfunctional host T cells and cooperate with host APC in antigen recognition, thereby leading to a reconstitution of T cell functions in vitro and in vivo and development of a stable, so far unprecedented, human T-T split chimera across MHC barriers.
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PMID:Coexistence of donor and host T lymphocytes following HLA-different bone marrow transplantation into a patient with cellular immunodeficiency and nonfunctional CD4+ T cells. 183 94

Functional studies were performed on human peripheral blood T lymphocytes stained with goat anti-5'-nucleotidase antibodies and separated into ecto-5'-nucleotidase (ecto-5'-NT)-positive and -negative populations using the FACSTAR fluorescence-activated cell sorter. On the average, ecto-5'-NT+ T cells contained 34 +/- 13% CD4+ and 55 +/- 15% CD8+ cells, whereas ecto-5'-NT-T cells contained 65 +/- 12% CD4+ and 23 +/- 8% CD8+ cells. Staining with anti-5'-NT antibodies did not significantly alter the ability of unseparated T cells to proliferate in response to PHA or PMA, or in a MLR. However, prior incubation with anti-5'-NT antibodies did inhibit the ability of irradiated T cells to provide help for PWM-stimulated Ig synthesis by as much as 55%. In five separate experiments, ecto-5'-NT-T cells demonstrated an equal or better ability to incorporate [3H]TdR after PHA stimulation or in a MLR, as compared with ecto-5'-NT+ T cells. Similarly, ecto-5'-NT- T cells were not diminished in their ability to provide help for autologous B cells in a PWM-driven system. Clearly, the inability of ecto-5'-NT- T cells from patients with a variety of immunodeficiency diseases to function in these assays cannot be explained solely by their lack of ecto-5'-NT activity. In contrast, ecto-5'-NT-positive and -negative T cells showed markedly different dose-response curves for proliferation in response to PMA. Ecto-5'-NT+ T cells responded to lower doses of PMA (1.0 ng/ml) than did ecto-5'-NT- T cells and showed a two- to eight-fold greater rate of [3H]TdR incorporation at 3 to 10 ng of PMA per ml. Ecto-5'-NT+ T cells may have a protein kinase C that is more accessible or more easily activated or may utilize an alternate pathway of activation when stimulated with low concentrations of PMA.
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PMID:Functional characterization of ecto-5'-nucleotidase-positive and -negative human T lymphocytes. 253 56

A case of the bare lymphocyte without apparent immunodeficiency was observed in a 33-year-old woman who had no history of severe infections but suffered from sino-bronchial disease. No HLA-A and -B antigens (class I antigens) were detected at the cell surface of lymphocytes, granulocytes, and platelets, but they were expressed, although at a reduced level, on the cultured B lymphoid cell line. T lymphocytes were normal in number and in the relative proportion of T4/T8 and responded to mitogens but not to PPD and candida. HLA-DR antigens (class II antigens) were present on B lymphocytes and showed intermediate MLR-stimulatory capacity, which made it possible to deduce the patient's HLA genotype. She was found to be homozygous at consanguinity for HLA-A, -B, and -DR antigens. The numbers of B lymphocytes, immunoglobulins, and complements were all in the normal range; there was, however, a low level of IgM. Two-dimensional gel analysis of class I antigens revealed the presence of normally expressed beta-2 microglobulins (B2M) and an apparently single set of class I heavy chains, allowing us to consider two alternative cellular mechanisms in this defect; the presence of one abnormal class I structural gene and the regulatory mechanism that acted in cis were suggested.
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PMID:Defective expression of HLA class I antigens: a case of the bare lymphocyte without immunodeficiency. 389 4

The autologous mixed lymphocyte reaction (AMLR) was studied in 18 patients with common variable immunodeficiency. The AMLR was decreased in 10 of 18 (55%) patients with common variable immunodeficiency compared to healthy controls. In allogeneic MLR, T cells from patients were found to be poor responders, and non-T cells poor stimulators, compared to allogeneic MLR between healthy normal controls. In allogeneic MLR, B cells (B cells + null cells) from patients were poor stimulators, whereas macrophages stimulated normally compared to controls. The deficient AMLR could be one of the mechanisms responsible for the increased risk of autoimmune phenomena in a subset of patients with primary immunodeficiency.
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PMID:Autologous mixed lymphocyte reaction in man. IV. Decreased autologous mixed lymphocyte culture response in patients with common variable immunodeficiency. 621 26

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

The characterization of restrictions to lentivirus replication in cells identifies critical steps in the viral life cycle and potential therapeutic targets. We previously reported that a human immunodeficiency virus type 2 (HIV-2) isolate was restricted to infection in some human cells, which led us to identify a step in the life cycle of HIV-2 detected after reverse transcription but prior to nuclear entry. The block is bypassed with a vesicular stomatitis virus glycoprotein G (VSV-G) envelope (A. McKnight et al., J. Virol. 75:6914-6922, 2001). We hypothesized that, although the restriction is apparent at a post-reverse transcription step, the lack of progress results from a failure of the virus to reach a cellular compartment with access to the nucleus. Here we analyzed molecular clones of the restricted virus, MCR, and an unrestricted virus, MCN. Using sequence analysis and gene swapping, we mapped the viral determinants to gag and env. Site-directed mutagenesis identified a single amino acid at position 207 in CA to be responsible for the gag restriction. Pseudotype experiments indicate that this step is also important for the infection of cells by HIV-1. The HIV-1 NL4.3 core is restricted if supplied with a restricted MCR envelope but not with VSV-G. Also the NL4.3 envelope rescues the restricted core of HIV-2 MCR. Abrogation experiments with MLV demonstrate that the restriction is distinct from Fv1/Ref1/Lv1. We propose that this represents a new lentiviral restriction, Lv2. Thus, the envelope and capsid of HIV act to ensure that the virus is delivered into an appropriate cellular compartment that allows postentry events in viral replication to proceed efficiently.
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PMID:Lv2, a novel postentry restriction, is mediated by both capsid and envelope. 1474 65

High affinity autoreactive IgG antibodies have been implicated in the development of lupus nephritis and other autoimmune disorders. With the discovery of activation-induced deaminase (AID), this question could be finally tested by examining the impact of AID deficiency in autoimmune-prone mice like the MLR/lpr strain. We have recently shown that AID-deficient MRL/lpr mice experienced a complete abrogation of lupus nephritis, and increased survival despite a dramatic increase in autoreactive IgM. Subsequent studies demonstrated that anti-dsDNA IgM is not pathogenic and in fact protects MRL/lpr from glomerulonephritis. AID-deficiency is also associated with decreased antibody-independent B cell-mediated autoimmunity likely through the loss of high affinity receptors through somatic hypermutation. Combined these results directly implicate AID in the development of B cell mediated autoimmunity. However, studies with hyper IgM AID-deficient patients indicate an increase in the incidence of certain autoimmunities. These results, likely the result of the immunodeficiency associated with AID deficiency, suggest caution in therapeutic approaches based in AID inhibition.
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PMID:The role of activation-induced deaminase in lupus nephritis. 2321 88


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