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)

Retroviral infections are accompanied by immunosuppression in a variety of species. For feline leukemia virus, the immunosuppression has been ascribed to the transmembrane envelope protein, p15E, which suppresses the proliferative responses of cat, mouse, and human lymphocytes. A similar suppressive effect has been shown for a lysate of human immunodeficiency virus (HIV), strain HTLV-IIIB. Here we determined that detergent-disrupted HTLV-IIIB lystate exerted a strong suppressive effect on PHA-stimulated lymphocytes. Preparations of whole virions, a lysate of a local HIV isolate grown on MP-6 cells, and a commercially obtained UV and psoralene-inactivated lysate were examined and demonstrated to have a similar suppressive effect. The HIV lysate was not directly cytotoxic to lymphocytes and did not contain tumor necrosis factor or lymphotoxin. The HIV lysate specifically suppressed the proliferation of a range of hemopoietic cell lines from man and mouse including three EBV transformed CD4- and IL-2 receptor-negative B-cell lines. The lysate also suppressed the formation of human bone marrow colonies, whereas the lysate had only a slight or no effect on fibroblasts. The suppression of lymphocyte proliferation was not abrogated by addition of IL-2 or IL-1 and the HIV lysate inhibited the expression of IL-2 receptors on suboptimal PHA-stimulated mononuclear cells. The suppressive factor(s) has not been characterized in molecular terms, but suppressive activity was recovered in fractions with a molecular weight of about 67,000 and in both the glycoprotein fraction and in the glycoprotein-depleted fraction of the HIV lysate. Sera from one-third of a small series (N = 13) of individuals with antibodies to HIV seem to be able to neutralize the suppressive properties of HIV lysate in cultures.
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PMID:Investigation of immunosuppressive properties of inactivated human immunodeficiency virus and possible neutralization of this effect by some patient sera. 278 62

In vitro differentiation and proliferation of precursor T-cells was examined in four homosexual men positive for anti-human immunodeficiency virus (HIV), one of whom had acquired immunodeficiency syndrome (AIDS). Peripheral mononuclear cells from the men were cultured with phytohemagglutinin-P in semi-solid culture media containing methylcellulose for 7 days. Colony formation was significantly reduced in all subjects, even in the presence of IL-2. Moreover, numerous colony component cells lacked T-cell specific surface markers. These results suggest that the impaired T-cell differentiation and proliferation occurs at the precursor T-cell level in HIV infection.
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PMID:T-cell colony formation in homosexual men with anti-human immunodeficiency virus. 278 90

The methodological aspects of Lak-cells functional activity test were determined. NK-resistance of P-815 culture cells and NK-sensitive K-562 cells were used as target cells. The highest cytotoxicity level was registered at the 5-th day of culturing MNC with rIL-2 at the final concentration (100 U/ml). The method developed was used for testing healthy donors group and group of patients with IL-2 dependent immunodeficiency (ophthalmic herpes). Data obtained show the significant decrease of LAK-cells functional activity of patients in comparison with healthy donors. Thus, the developed method is recommended for complex estimation of immune status of patients with IL-2-dependent immuno deficiency.
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PMID:[Assessment of the functional activity of lymphokine-activated killer cells in healthy donors and in patients with interleukin-2-dependent immunodeficiency]. 279 Jan 70

In 1911, the first retrovirus was described: the Rous sarcoma virus, an avian retrovirus. Forty years later the murine leukemic virus, a mouse retrovirus, was reported. Although many other retroviruses from non-primate species were identified during the 1960s, the first primate retrovirus was not recognized until it was isolated from a monkey tumor in 1970. The search for human retroviruses in human leukemic cells remained unsuccessful at that time. Facilitated by the discovery of T-cell growth factor, a substance used for the propagation of human leukocytes in cultures, the first human retrovirus was discovered in 1980. Soon thereafter, in 1983, another human retrovirus, human immunodeficiency virus (HIV), was reported and implicated as the etiologic agent of AIDS. The isolation and identification of HIV has stimulated much interest in the study of human retroviruses and the control of this new viral disease.
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PMID:Perspectives on retroviruses and the etiologic agent of AIDS. 282 49

The GvH reaction resulting from the injection of parental strain cells into adult F1 hybrids suppresses both cell-mediated and humoral immune responses and is dependent on the donor-host combination and the number of parental cells used to induce the GvH reaction. The early suppression is due, at least in part, to the increased number of macrophages and the activation of suppressor macrophages which act directly on the T-helper cell and perhaps the B-cell as well. The macrophage suppression is associated with an increase in PGE production. The long-term T-cell immunodeficiency is mediated by GvH-induced thymic dysplasia resulting in a block or an arrest in T-cell differentiation and deficient IL-2 production. The B-cell immunodeficiency is associated with both a decrease in B-cell production from lymphoid progenitors and a decrease in CFU-s production. The GvH reaction induces 2 types of thymic lesion, a stress-related effect causing atrophy of the thymic cortex and a cytolytic process causing severe-to-moderate lesions in the thymic medulla as a consequence of injury to medullary epithelial cells and a loss of Hassall's corpuscles (thymic dysplasia). By employing the NK-cell-deficient beige mutation, it was shown that the severe-to-moderate thymic medullary lesions occurred in F1 mice only in those transplant situations in which the donor inoculum was of the +/bg genotype, regardless of the genotype of the recipient. It is proposed that activation of parental T cells may contribute to the early immunosuppressive events; however, the relatively permanent immunosuppression appears to be associated with NK-like effector cells which are capable of causing injury to lymphoid and epithelial tissue, especially epithelium of the thymic medulla. These studies raise the possibility that the GvH reaction may contribute to some T- and B-cell immunodeficiencies observed in the SCID and AIDS syndromes, as well as in patients following bone marrow transplantation.
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PMID:The functional and histological basis for graft-versus-host-induced immunosuppression. 293 84

The expression of Fc epsilon R on human lymphocytes was studied with the anti-Fc epsilon R mAbs. Fc epsilon R was expressed on most mu+,delta+ circulating B cells, whereas T cells did not express Fc epsilon R even in patients with hyper-IgE syndrome. B cells with gamma, alpha, or epsilon phenotype did not express Fc epsilon R, moreover its expression could not be induced, suggesting that the Fc epsilon R expression was correlated with isotype switching. mu+delta+ B cells in bone marrow did not express Fc epsilon R, but PHA-sup (supernatant from PHA-stimulated cell cultures) could induce its expression, and the addition of IgE augmented this induction. Recombinant IL-2, IL-1, IFN-gamma or -beta, or purified B cell differentiation factor (BSF-2 B cell-stimulatory factor 2) could not induce Fc epsilon R expression in bone marrow B cells. IFN-gamma inhibited the Fc epsilon R expression induced by PHA-sup, suggesting that the human counterpart of BSF-1 may be responsible for Fc epsilon R expression in bone marrow B cells. B cells from patients with common variable immunodeficiency and ataxia telangiectasia did not express Fc epsilon R, but PHA-sup could induce its expression, indicating that circulating B cells of these patients are at a differentiation stage similar to B cells in bone marrow. The study showed that Fc epsilon R is a B cell-specific differentiation marker, the expression of which is restricted to a defined stage of B cell differentiation.
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PMID:Fc epsilon receptor, a specific differentiation marker transiently expressed on mature B cells before isotype switching. 294 90

A new trypsin-like serine protease was cloned from both a murine cytotoxic T lymphocyte and a human PHA-stimulated peripheral blood lymphocyte cDNA library. In both the mouse and human system, this transcript had a T cell- and NK-specific distribution, being detected in cytotoxic T lymphocytes (CTL), some T-helper clones, and NK, but not in a variety of normal tissues. T-cell activation with Con A plus IL-2 induced mouse spleen cells to express this gene with kinetics correlating with the acquisition of cytolytic capacity. Both the mouse and human nucleotide sequences of this gene encoded an amino acid sequence with 25-40% identity to members of the serine protease family. The active-site "charge-relay" residues (His-57, Asp-102, and Ser-195 of the chymotrypsin numbering system) are conserved, as well as the trypsin-specific Asp (position 189 in trypsin). We reviewed the evidence of this serine protease's role in lymphocyte lysis and proposed a "lytic cascade." We discussed the biological and clinical implications of a cascade, proposing these enzymes as markers for cytolytic cells and as targets for rational drug therapy. Genetic and acquired deficits in the lethal hit-delivery system are considered as a basis for approaching some immunodeficiency states, including severe EBV infections, T-gamma leukemias, and T8+ lymphocytosis syndromes.
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PMID:A T cell- and natural killer cell-specific, trypsin-like serine protease. Implications of a cytolytic cascade. 305 12

The cell interactions that take place between Toxoplasma gondii trophozoites and the human immune system have been investigated by using an in vitro model of infection. PBMC were co-cultured with live, appropriately attenuated, trophozoites. When cells from immune (seropositive) donors were used, a proliferative response was observed. At the same time, the proliferating T cells proved capable of controlling the growth of live trophozoites. By contrast, cells from seronegative donors failed to mount a proliferative response and intracellular overgrowth of trophozoites with subsequent cell injury occurred. Actively proliferating T cells were expanded in continuous cell lines with IL-2 and periodical restimulation with Ag in the presence of autologous irradiated mononuclear cells. From some of the lines obtained, clones were also derived. Ten clones were selected for further studies. They proliferated in response to trophozoites but not to unrelated Ag. Their response required the presence of autologous monocytes-macrophages isolated from peripheral blood on Percoll density gradients. B cells that were obtained from the same donors and immortalized by EBV infection proved inefficient as APC. These data suggest that live trophozoites have to be processed by macrophages in order to be presented to T cells. Upon appropriate antigen stimulation, all of the clones produced IL-2 and IFN-gamma, a finding that was consistent with both their CD4+ surface phenotype and their helper capacity on B cell proliferation and differentiation in vitro. The supernatants of all of the stimulated clones released a factor that activated macrophages to kill intracellular trophozoites as well as an unrelated pathogen, Listeria monocytogenes. This factor was identified as IFN-gamma because it was neutralized by specific anti-IFN-gamma antibodies. The present in vitro model of response to live protozoa may prove suitable to assess the role of both T lymphocytes and macrophages in intracellular parasite infections in man. Furthermore, this experimental system may be applied to detect specific lesions of cell mediated immunity in a number of immunodeficiency syndromes.
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PMID:An in vitro model for Toxoplasma infection in man. Interaction between CD4+ monoclonal T cells and macrophages results in killing of trophozoites. 312 96

Human immunodeficiency virus (HIV) envelope glycoprotein is synthesized as a polyprotein precursor of 160 kDa (gp 160) and is subsequently cleaved into an amino terminus subunit, gp 120, and a carboxyl terminus transmembrane subunit, gp 41. Two synthetic peptides corresponding to amino acid sequences 735-752 and 846-860, respectively, as deduced from the nucleotide sequence of HTLV-IIIB gp 160 were synthesized and used to assess their effects on normal human lymphocyte blastogenesis. Peptides 735-752 and 846-860 conjugated to protein carriers, but not free peptides, exerted a pronounced suppression of the normal human lymphocyte proliferative response to concanavalin A (Con A), phytohemagglutinin (PHA), pokeweed mitogen (PWM), and alloantigens. A synthetic peptide homologous to a 17 amino acid sequence of the gene product of HIV trans-acting transcriptional (TAT III) gene had no suppressive effects. Peptides 735-752 and 846-860 also inhibited the IL-2-dependent proliferation of the murine CTLL-2 cell line and the PHA-induced proliferation of normal mouse spleen cells. HIV peptide-induced suppression of human blastogenesis required a 2- to 3-day incubation of responder cells with peptides, suggesting that binding of peptides to the cell membrane was not sufficient for suppression. These results suggest that, in addition to the selective cytopathic effects of HIV, the etiological agent of the acquired immunodeficiency syndrome (AIDS), on the T-helper/inducer lymphocyte subset, viral peptide-mediated immunosuppression may also play an important role in the pathogenesis of the disease. Moreover, these data clearly indicate the need to address the potential immunosuppressive property of HIV antigens in the effort to select and develop effective prophylactic means against AIDS.
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PMID:Synthetic peptides homologous to HIV transmembrane glycoprotein suppress normal human lymphocyte blastogenic response. 325 17

Hodgkin's disease (HD) is an aggressive human lymphoproliferative disease that displays a curious pleomorphic histopathologic appearance unlike that of any of the common non-Hodgkin's lymphomas (NHL). Although the bizarre giant cells of the HD lesion, the Reed-Sternberg cells (RSC) and mononuclear variant Hodgkin's cells (HC), have been considered to be malignant cells, little objective evidence supports this conclusion. We have studied the proliferative characteristics of T cell as well as RSC and HC-enriched populations from HD lesions, and found the majority of the proliferative activity in the T cell populations. RSC-enriched populations not only showed little spontaneous proliferation, but also did not respond to a variety of cytokine growth factors in vitro, suggesting that these cell populations are not actively growing cells. Further molecular studies to identify possible monoclonal T or B cell populations in HD lesions, using a TCR beta chain probe and IgH probes respectively on Southern blot analysis, revealed no evidence of monoclonal lymphoid cell populations. Additional studies on the characteristic T cell immunodeficiency in HD were also undertaken. Our previous studies had associated a decrement in IL-2 production with this defect. Our studies now show that an intrinsic T cell abnormality exists when HD patients' T cells are stimulated with agonistic MAb that can optimally activate and stimulate IL-2 production in normal control T cells.
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PMID:In vitro analysis of cell populations involved in Hodgkin's disease lesions and in the characteristic T cell immunodeficiency. 326 Dec 71


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