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

Brucella abortus may be useful as a component of vaccines. This is because it possesses several unique properties as a carrier that enable it to stimulate human B cells even in the relative absence of T cells. Human immunodeficiency virus type 1 proteins conjugated to B. abortus could induce neutralizing antibodies against human immunodeficiency virus type 1. Recently we showed that the characteristics of lipopolysaccharide (LPS) derived from B. abortus are similar to those of the whole bacterium in that the LPS acts as a T-independent type 1 carrier in mice. In this study we wanted to determine whether LPS derived from B. abortus is associated with the adverse effects seen with other bacterial endotoxins. LPS purified from B. abortus by butanol extraction was shown to have less than 2% (wt/wt) contamination by protein and less than 1% (wt/wt) contamination by nucleic acids and to contain 1% (wt/wt) ketodeoxyoctanic acid. Compared with LPS derived from Escherichia coli, B. abortus LPS was 10,000-fold less potent in eliciting fever in rabbits, 268-fold less potent in killing D-galactosamine-sensitized mice, and 1,400-fold and 400-fold less potent in inducing interleukin-1 beta and tumor necrosis factor alpha production, respectively. These results suggest that B. abortus LPS is much less likely than the LPS from E. coli to evoke endotoxic shock; therefore, it may be feasible to incorporate B. abortus as a component of vaccines.
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PMID:Lipopolysaccharide (LPS) from Brucella abortus is less toxic than that from Escherichia coli, suggesting the possible use of B. abortus or LPS from B. abortus as a carrier in vaccines. 154 64

In the present study inactivated human immunodeficiency virus type 1 (HIV-1) was conjugated to Brucella abortus and tested for immunogenicity in normal and anti-L3T4-treated BALB/c mice. HIV-BA was more immunogenic than uncoupled HIV in normal mice, since 6-fold less virus in HIV-BA preparations elicited higher titer responses than HIV-1 alone. Furthermore, the HIV-BA antibody response reached higher levels before the HIV-1 response. Immunoblot analysis showed that most of the HIV-1 antigens were recognized by antibodies induced by either HIV-1 or HIV-BA. Isotype analysis revealed that HIV-1 induced similar levels of IgG1 and IgG2a antibodies, whereas the IgG2a responses to HIV-BA were more pronounced than the IgG1 response. These different IgG subclass patterns suggest that conjugation of HIV-1 to BA changed the immunogenic nature of HIV-1. The requirement for helper T cells was examined by immunizing mice that were depleted of CD4+ T cells by in vivo anti-L3T4 treatment. Under these conditions the IgG responses to HIV-1 were completely eliminated. Although HIV-BA antibody responses were markedly reduced in anti-L3T4-treated mice, anti-HIV-1 antibodies, mainly of the IgG2a isotype, were produced. The antibodies generated by HIV-1 and HIV-BA immunization were also tested for their ability to inhibit syncytia formed by infecting CD4 + CEM cells with gp160 vaccinia. Sera from normal mice, immunized with either HIV-1 or HIV-BA were capable of inhibiting syncytia. In contrast, following anti-L3T4 treatment, only mice immunized with HIV-BA, but not HIV-1, produced antibodies capable of inhibiting syncytia.
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PMID:Production of a novel antigen by conjugation of HIV-1 to Brucella abortus: studies of immunogenicity, isotype analysis, T-cell dependency, and syncytia inhibition. 167 17

The origins of retrovirology began in the primordial laboratories of Ellermann and Bang and of Rous in the first decade of the twentieth century. More than 40 frustrating years were to elapse before this early work with chickens was to lead to experiments with mice, made possible by the use of inbred strains and catalyzed by the observations of Dalldorf and of Gross that newborn animals were susceptible targets for pathogenesis by, respectively, Coxsackie viruses, and polyoma and retroviruses. Seminal observations by Charlotte Friend that retroviruses caused neoplasia in adult mice and her studies investigating the properties and pathogenesis of the Friend leukemia virus, as well as the role of the host immune response in development of disease, helped lay the groundwork of modern retrovirology. The use of retroviruses to study cell differentiation became the foundation on which many more recent discoveries rest. Above all, the information supplied by Friend and her colleagues and investigators in other laboratories finally enabled unequivocal isolation of the first human retroviruses long after most investigators had given up hope of finding such agents in man. Moreover, the techniques developed and the rapid characterization of these newly discovered human pathogens enabled the isolation of human immunodeficiency virus, the cause of acquired immunodeficiency syndrome. It is a challenge to current investigators to extend and expand upon the original work of Friend concerning the pathogenesis of retroviruses, as only a fuller understanding of the complex virus-host disease patterns induced by these viruses will ultimately lead to their control and prevention.
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PMID:The Friend legacy: from mouse to man. 267 24

A well-characterized murine model of graft-vs-host disease (GVHD) that develops in response to minor histocompatibility antigens was used to study the mechanism of an immunodeficiency syndrome that is associated with GVHD. Lethally irradiated mice were transplanted with a combination of bone marrow and spleen cells from H-2 compatible donors that differed at multiple minor histocompatibility antigens, or from syngeneic donors. Four to 12 weeks later, the humoral responses of transplanted and control mice to the T dependent antigens bacteriophage phiX174 and TNP-sheep red blood cells (TNP-SRBC), and to the T independent antigen TNP-Brucella abortus (TNP-BA) were determined. The results demonstrate that mice with GVHD have relatively intact B Cell function and a profound defect in T helper cell function. The immune response to T dependent antigens normalized with repeated immunization. We conclude that immune dysfunction in mice with GVHD is due to a reversible defect in T helper cell function.
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PMID:Mechanism of immune dysfunction associated with minor antigen graft-vs-host disease in mice. 297 64

Mice were given single injections of sheep erythrocytes (SE) or polyvinylpyrrolidone (PVP) at various times after sublethal, whole-body irradiation (550 rad 60CO) and direct, antigen-specific, plaque-forming cell (PFC) responses were quantified. Irradiated mice did not respond to SE or PVP when immunized 15 d postirradiation (PI); by day 30 PI, the responses by irradiated mice were 40-126% of normal to SE and 3-38% of normal to PVP. The impaired recovery after irradiation of immune responses to PVP was not due to altered antigen dose requirements or altered time of peak PFC response and occurred after irradiation of mice by doses as low as 200 rad. Both athymic and euthymic mice had impaired responses to PVP after whole-body irradiation. The impaired response of irradiated mice to PVP was repaired by adoptive transfer of normal bone marrow, fetal liver, or spleen cells and also by spleen cell preparations enriched in Ig+ cells but not by spleen cell preparations enriched in Thy.1+ or Ig- cells. With the aid of additional antigens it was observed that by day 30 PI, mice had recovered ability to respond to the T-cell-dependent antigen SE and the T-cell-independent type-1 antigens 2,4,6-trinitrophenyl-Brucella abortus and butanol-extracted bacterial lipopolysaccharide, but at that time they gave impaired responses to the T-cell-independent type-2 antigens PVP, type III pneumococcal polysaccharide, and phenol-extracted bacterial lipopolysaccharide; they had an immune response pattern similar to that of CBA/N mice having an X-linked immunodeficiency.
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PMID:Differential recovery of antibody production potential after sublethal, whole-body irradiation of mice. 352 64

We have previously shown that immunization of mice with human immunodeficiency virus (HIV)-derived proteins or peptides conjugated to inactivated Brucella abortus induces the secretion of virus-neutralizing antibodies, predominantly of the immunoglobulin G2a (IgG2a) isotype. In addition, B. abortus activates human CD4+ and CD8+ cells to secrete gamma interferon. Since these are both characteristics of a Th1-type immune response, which is associated with the development of cell-mediated immunity, it was important to determine if B. abortus conjugates would also act as a carrier to induce a cytotoxic T-lymphocyte (CTL) response. To test this hypothesis, we conjugated an 18-amino-acid peptide from the V3 loop of the MN strain of HIV-1 gp120 that contains both B- and cytotoxic T-cell epitopes to B. abortus (B. abortus-MN 18-mer). A 10-amino-acid fragment of this peptide has been shown to be the minimal CTL determinant presented by murine H-2Dd. It was found that two in vivo immunizations with 10(8) organisms of B. abortus-MN 18-mer followed by in vitro stimulation with peptide induced a virus-specific CTL response. Conjugation to B. abortus was required for in vivo priming, since there was no induction of memory CTLs when B. abortus was only mixed with peptide. Targets pulsed with peptide as well as those infected with a vaccinia virus encoding HIV gp160 were killed, demonstrating recognition of naturally processed envelope. Also, major histocompatibility complex-incompatible L cells which were infected with vaccinia viruses that encoded H-2Dd, but not H-2Kd, and pulsed with peptide were lysed. This demonstrated the appropriate major histocompatibility complex class I restriction. Treatment of the mice with anti-L3T4 prior to immunization caused a severe depletion of CD4+ lymphocytes, yet it did not decrease the CTL priming. Thus, inactivated B. abortus can induce non-CD4+ cells to produce the cytokines required for CTL induction. We conclude that B. abortus stimulates a cellular as well as a humoral immune response, even in the relative absence of CD4+ helper cells. It may be a particularly useful vaccine carrier in HIV-1-infected individuals or others with impaired CD4+ T-cell function.
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PMID:Brucella abortus conjugated with a peptide derived from the V3 loop of human immunodeficiency virus (HIV) type 1 induces HIV-specific cytotoxic T-cell responses in normal and in CD4+ cell-depleted BALB/c mice. 862 87

Human (HIV) and feline (FIV) immunodeficiency virus has been reported to infect bone marrow (BM) and stroma, followed by a loss in normal hematopoiesis. However, the magnitude and nature of HIV and FIV pathogenesis of the BM/stromal network are still unclear. In the current studies, pathogenesis of stromal cells was evaluated using the FIV model. Fourteen specific-pathogen-free cats inoculated with the four different strains (FIV(UK8), FIV(Bang), FIV(Shi), or FIV(Pet)) were monitored for FIV infection in the peripheral blood mononuclear cells (PBMC), BM cells, and stromal cells. All inoculated cats became positive for FIV in the PBMC by 7 weeks p.i. and 13 of 14 cats had FIV in the BM cells by 7-13 weeks p.i. FIV was detected in macrophages and stromal fibroblasts from FIV(UK8)-, FIV(Bang)-, and FIV(Shi)-infected cats but not from FIV(Pet)-infected cats and only transiently in cells from FIV(Shi)-infected cats. The ability of the supernatants from FIV-infected stromal cells to sustain the growth of uninfected BM cells was decreased 35-46% when compared to the supernatants from uninfected stromal cells. These results suggest that the FIV infection of the stroma alters normal hematopoietic function(s) and that the infected stromal cells can also serve as a reservoir for FIV infection.
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PMID:Phenotypic and functional characteristics of FIV infection in the bone marrow stroma. 1125 95

Heat-killed Brucella abortus (HBa) has been proposed as a carrier for therapeutic vaccines for individuals with immunodeficiency, due to its abilities to induce interleukin-2 (IL-2) and gamma interferon (IFN-gamma) in both CD4(+) and CD8(+) T cells and to upregulate antigen-presenting cell functions (including IL-12 production). In the current study, we investigated the ability of HBa or lipopolysaccharide isolated from HBa (LPS-Ba) to elicit beta-chemokines, known to bind to the human immunodeficiency virus type 1 (HIV-1) coreceptor CCR5 and to block viral cell entry. It was found that human peripheral blood mononuclear cells secreted beta-chemokines following stimulation with HBa, and this effect could not be blocked by anti-IFN-gamma neutralizing antibodies. Among purified T cells, macrophage inflammatory protein 1alpha and 1beta (MIP-1alpha and MIP-1beta, respectively) secretion was observed primarily in human CD8(+) T cells. The kinetics of beta-chemokine induction in T cells were slow (3 to 4 days). The majority of beta-chemokine-producing CD8(+) T cells also produced IFN-gamma following HBa stimulation, as determined by triple-color intracellular staining. A significant number of CD8(+) T cells contained stored MIP-1beta that was released after HBa stimulation. Both HBa and LPS-Ba stimulated high levels of MIP-1alpha and MIP-1beta production in elutriated monocytes and even higher levels in macrophages. In these cells, beta-chemokine mRNA was upregulated within 30 min and proteins were secreted within 4 h of stimulation. The monocyte- and macrophage-derived beta-chemokines were sufficient to block CCR5-dependent HIV-1 envelope-mediated cell fusion. These data suggest that, in addition to the ability of HBa to elicit antigen-specific humoral and cellular immune responses, HBa-conjugated HIV-1 proteins or peptides would also generate innate chemokines with antiviral activity that could limit local viral spread during vaccination in vivo.
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PMID:Human peripheral blood T cells, monocytes, and macrophages secrete macrophage inflammatory proteins 1alpha and 1beta following stimulation with heat-inactivated Brucella abortus. 1134 47

The antiviral activity of recombinant feline interferon-gamma (rFeIFN-gamma) against feline immunodeficiency virus (FIV) was investigated. A persistently FIV(Bang)-infected feline T cell line (FeT-J/Bang) was treated with either rFeIFN-omega, rFeIFN-gamma, or recombinant human IFN-alpha2 (rHuIFN-alpha2), and the culture fluids were tested for antiviral activity by reverse transcriptase (RT) assay. FeT-J/Bang cell cultures treated with rFeIFN-omega showed dose-dependent inhibition of RT activity. In contrast, rFeIFN-gamma treatment had no antiviral effect on FIV replication but instead caused a statistically significant enhancement on day 9 of culture. Antiviral activity of rFeIFN-gamma was also tested on feline peripheral blood mononuclear cells (PBMC). PBMC cultures were inoculated with FIV(Bang) and simultaneously treated with either rFeIFN-omega, rFeIFN-gamma, or rHuIFN-alpha2. FeIFN-gamma had no effect on FIV replication, unlike the rFeIFN-omega and rHuIFN-alpha2, which had strong anti-FIV effects. In another study, rFeIFN-gamma treatment was initiated 3 days before FIV(Bang) infection, the day of FIV(Bang) infection, or 3 days post-FIV(Bang) infection and then tested for antiviral activity. The time of initiating rFeIFN-gamma treatment had no effect on the antiviral activity. Hence, these results suggest that unlike rHuIFN-alpha2 and rFeIFN-omega, rFeIFN-gamma has no inhibitory effect on FIV replication in PBMC but causes a slight enhancement in a feline T cell line.
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PMID:Feline immunodeficiency virus lacks sensitivity to the antiviral activity of feline IFN-gamma. 1179 61