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)

Efforts to generate a vaccine to prevent infection by human immunodeficiency virus (HIV) have focused on inducing neutralizing antibodies. However, cytotoxic T-lymphocyte (CTL) responses are a major immune defense mechanism required for recovery from many different virus infections. Since CTL epitopes can be defined by short synthetic peptides, we searched for HIV peptides that elicit a viral-specific CTL response in mice. We have developed a new method for screening CTL-inducing peptides involving a single injection into the footpad of mice to prime CTLs in the draining popliteal lymph node of mice within 10 days. Our results demonstrate that a 15-amino acid peptide (aa 315-329) derived from the V3 loop of HIV gp120 caused a rapid induction of peptide-specific and gp160-specific CD8-positive CTLs. Lysis of targets is specific since cells preincubated with unrelated peptides are resistant to lysis as are cells of a different MHC haplotype pretreated with the cognate peptide. Pretreatment of restimulated node cells with complement plus anti-CD8 but not anti-CD4 removed the lytic activity. We also successfully induced in vivo CTL activity with unmodified synthetic peptides from the influenza and Sendai virus nucleoproteins, indicating general applicability of our method for rapid screening of CTL epitopes. Because HIV replication has been reported by several labs to occur mainly in lymph nodes of infected patients, the rapid induction of HIV-specific CTLs in proximal lymph nodes by unmodified peptides emphasizes the physiological significance of our findings toward vaccine and therapeutic approaches.
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PMID:Rapid in vivo induction of HIV-specific CD8+ cytotoxic T lymphocytes by a 15-amino acid unmodified free peptide from the immunodominant V3-loop of GP120. 131 70

The initial step in the infection cycle of human immunodeficiency virus type 1 (HIV-1) involves binding of its surface glycoprotein gp 120 to the T lymphocyte CD4 antigen. CPF-DD is a low molecular weight inhibitor of HIV infectivity that inhibits gp 120 binding to CD4 in vitro (Finberg et al., Science 249, 287-291, 1990). We find, however, that the actions of CPF-DD are not limited to its ability to interfere with gp 120-CD4 binding; its predominant action is to remove the viral envelope from the underlying core. Subsequently the virions disintegrate. Most enveloped viruses tested were inhibited by CPF-DD, but the infectivity of noneneloped viruses was unaffected or only slightly reduced.
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PMID:CPF-DD is an inhibitor of infection by human immunodeficiency virus and other enveloped viruses in vitro. 131 72

The CD4 protein expressed on helper T lymphocytes is a restriction element for major histocompatibility class II immune responses. This molecule is also used by the human immunodeficiency virus as its specific cellular receptor facilitating binding of virus to cells. As soluble forms of CD4 inhibit HIV infection in tissue culture, attention has focused on this molecule. Bacterially produced CD4 would facilitate studies of the biology of the CD4 molecule. However, bacterially expressed CD4 must be refolded for assumption of its interaction with conformationally dependent anti-CD4 monoclonal antibodies as well as the HIV-1 envelope protein gp120. We report here the engineering of an external domain construct of the CD4 gene into a novel expression vector containing the nucleotide sequence encoding the pelB leader peptide of Erwinia carotovara (pDABL), to facilitate correct folding of CD4 in bacteria. Monoclonal antibodies specific for important conformational epitopes of the CD4 molecule were able to bind bacterial colonies containing the pDABL/CD4 vector but not colonies with vector alone. Importantly, recombinant gp120 produced in baculovirus bound specifically to bacterial colonies expressing the CD4 recombinant molecule. This system presents a simple screening mechanism for molecules that bind to the external domain of the CD4 glycoprotein. Vectors such as pDABL will also facilitate the production of large amounts of biologically active proteins in bacteria.
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PMID:Construction of a recombinant bacterial human CD4 expression system producing a bioactive CD4 molecule. 131 11

We investigated the effects of two behavioral interventions--aerobic exercise and cognitive behavioral stress management (CBSM)--on Epstein-Barr virus viral capsid antigen (EBV-VCA) and human herpesvirus type-6 (HHV-6) antibody modulation in 65 asymptomatic gay men measured at several time points in the 5 weeks preceding and following notification of their human immunodeficiency virus-type 1 (HIV-1) serostatus. After accounting for potential immunomodulatory confounds, we found that HIV-1 seropositive men had higher EBV-VCA antibody titers than those diagnosed as seronegative at every time point during the study; however, no significant differences were found with respect to HHV-6. Among HIV-1 seropositive and seronegative subjects, respectively, those randomized to either behavioral intervention had significant decreases in both EBV-VCA and HHV-6 antibody titers over the course of the intervention as compared with assessment-only controls (of HIV-1 seropositive and seronegative status) whose antibody titers did not significantly change and which remained consistently higher than either serostatus-matched intervention group over subsequent time points, independent of total immunoglobulin G levels and degree of polyclonal B cell activation. In attempting to explain serostatus differences in EBV and HHV-6 values, it was found that HIV-1 seropositive men had significantly lower CD4 cells, CD4:CD8 ratio, and blastogenic response to phytohemagglutinin (PHA), as well as significantly higher CD8 cells at baseline. No significant differences were found between the HIV-1 seropositive and seronegative men with respect to anxiety and depression at baseline. Since the greatest changes in EBV and HHV-6 occurred between baseline and week 10, we correlated changes in immune (CD4, CD8, CD4:CD8 ratio, PHA stimulation) and distress-related markers (state depression and anxiety) with EBV and HHV-6 change scores over this time period. No significant correlations were found between any of these immune- or distress-related variable and the antibody change scores suggesting that the mechanisms by which EBV and HHV-6 antibodies are being modulated by these interventions possibly involve other, yet to be determined, immune, neuroendocrine, and/or psychologic variables.
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PMID:Psychosocial modulation of antibody to Epstein-Barr viral capsid antigen and human herpesvirus type-6 in HIV-1-infected and at-risk gay men. 132 Feb 79

Expression of CD4, CD8, IL-2 receptor alpha chain (IL-2R alpha), and MHC class II (MHC-II) on peripheral blood mononuclear cells were examined in cats infected with feline immunodeficiency virus (FIV). CD4/CD8 T cell ratio in FIV-infected cats was slightly decreased, as compared with that in specific-pathogen-free (SPF) cats. However, there was no statistical differences between them. The number of circulating IL-2R alpha+ cells in FIV-infected cats was higher than that in healthy cats, whereas induction of IL-2R alpha expression by concanavalin A (Con A) stimulation was depressed in FIV-infected cats. By using two-color cytofluorometry, Con A-induced enhancement of IL-2R alpha expression was found to be reduced in both CD4+ and CD8+ populations in PBMC from FIV-infected cats. The circulating MHC-II+ cells were also increased in FIV-infected cats. Furthermore, the induction of IL-2R alpha expression on PBMC after Con A-stimulation significantly depressed by FIV inoculation in vitro. These results suggest that FIV activates PBMC in vivo via direct and/or indirect mechanisms, leading to the unresponsive state of T cells to further stimuli in vitro.
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PMID:Altered surface antigen expression on peripheral blood mononuclear cells in cats infected with feline immunodeficiency virus. 132 15

Disseminated toxoplasmosis, one of the most severe acquired immune deficiency syndrome (AIDS)-associated infections in humans, is believed to develop from a latent infection after the cellular immune system is suppressed by human immunodeficiency virus type 1 (HIV-1). However, Toxoplasma gondii may serve as a cofactor in enhancing the immunodeficiency induced by HIV-1. This hypothesis is supported by the facts that: 1) co-infection with other pathogens in humans infected with HIV-1 may enhance the progression of the disease to AIDS; and 2) concomitant infection with T. gondii enhances feline immunodeficiency virus-induced immune dysfunction and is likely to cause a more rapid disease onset than an infection with HIV alone. It is possible that T. gondii infection induces tumor necrosis factor (TNF) production. TNF then stimulates the induction of T-cell proteins that bind to the long terminal repeat of HIV-1. This binding at the repeat site then leads to increased HIV-1 activation which causes the dysfunction of CD4 cells and a resulting immunodeficiency that allows even greater amounts of T. gondii replication.
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PMID:Toxoplasma gondii: an AIDS enhancing cofactor. 133 11

Two immature T cell lines (FT1 and FT4) were established after in vitro cloning of peripheral blood lymphocytes (PBLs) from an asymptomatic human immunodeficiency virus type 1 (HIV-1) seropositive, human T cell-lymphotropic virus type 1 seronegative homosexual subject. Although derived from a limiting dilution cell cloning assay, these cell lines were not recloned for this study. Their growth was independent of exogenous interleukin-2. Both cell lines were able to form colonies when cloned in agar, but failed to form solid tumours when injected into nude mice. FT lines belong to the very immature T cell lineage as they exhibit rearranged TCR genes but no expression of T cell membrane antigens, including CD2, CD3, CD4, CD6, CD7 and CD8. They also contain an HIV-1 genome that was detected only in an extra-chromosomal DNA form, even after several passages in vitro. The presence of unintegrated viral DNA was also detected by polymerase chain reaction analysis in the same sample of fresh uncultured PBLs. Furthermore, despite the absence of CD4 expression, both T cell lines were susceptible to CD4-independent HIV-1 superinfection (lack of superinfection inhibition in the presence of OKT4A monoclonal antibodies).
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PMID:Extrachromosomal human immunodeficiency virus type 1 DNA forms in fresh peripheral blood lymphocytes and in two interleukin-2-independent T cell lines derived from peripheral blood lymphocytes of an asymptomatic seropositive subject. 133 22

Seven immortalized B cell clones, five of which secreted specific human monoclonal antibodies (MAbs) against hepatitis B, tetanus toxoid, and Rhesus D antigens, were evaluated for their susceptibility to infection by human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Infection was confirmed in three human MAb-producing lines by detection of infectious virus and p24 antigen in culture supernates, by immunofluorescence, and by detection of viral DNA in cells by polymerase chain reaction. The infectable lines were as susceptible to HIV-1 infection as several T cell lines and remained persistently infected for several months, but in contrast to T cell controls, viral cytopathic effects were not observed. Levels of unintegrated viral DNA in the HB1 B cell line were significantly lower than in the HUT78 T cell line. Cell lines that were susceptible to HIV expressed HLA DR, CD20, and CD21, whereas the uninfectable cell lines did not express any of the markers tested. CD4 was undetectable or present on a small percentage of cells in two of the infectable cell lines. However, infection with HIV-1 was blocked more efficiently in B cells than in T cells by soluble CD4, anti-CD4 MAb, and dextran sulphate. The effect of HIV infection on human MAb secretion was variable, being reduced on a per-cell basis in one line, increased in another, and unchanged in a third.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Susceptibility of human monoclonal antibody-producing B cell lines to infection by human immunodeficiency virus. 133 86

This study demonstrates the transmission of feline immunodeficiency virus (FIV) from infected queens to kittens in two separate litters. Queen 1 was infected by intravenous administration of FIV at 22 days prior to parturition. Two out of three kittens from the litter were found to be viremic at 10 weeks of age as detected by culture isolation and polymerase chain reaction detection of FIV DNA in peripheral blood mononuclear leukocytes. The third kitten remained aviremic through 40 weeks of age. Queen 2 was infected by subcutaneous administration of FIV 2 days prior to parturition. This litter also had two out of three kittens infected with FIV; however, viremia was not detected in one of the kittens until 21 weeks of age. Culture isolation was found to be superior to polymerase chain reaction for the early detection of FIV, and viremia was found to precede seroconversion by up to 4 weeks. Although all infected kittens have remained healthy, depressed CD4:CD8 lymphocyte ratios suggest that clinical disease may develop. This study suggests that FIV infection in cats may be a useful model system for the study of HIV transmission from mothers to infants.
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PMID:Transmission of feline immunodeficiency virus from infected queens to kittens. 133 4

Patients after bone marrow transplantation are immunodeficient for months to years. To understand better the pathogenesis of this immunodeficiency, we studied quantitative reconstitution of blood monocytes, natural killer (NK) cells, T cells, and B cells at 2-22 months post-transplant. The results indicate monocyte and NK counts generally recover within 2 months, followed by CD4-CD8+ T cell, B cell, and finally (after > 1 year) CD4+CD8- T cell numbers. Dual-positive CD4+CD8+ T cells (which were barely detectable in normal adults), CD4-CD8+ T cells and B cells transiently reached supranormal levels during recovery. Both CD4+CD8- and CD4-CD8+ T cells were larger than controls throughout the 2-year follow up. Comparison with neonatal and infant mononuclear cell subsets suggested the reconstitution of CD4+CD8+ T cells and B cells is similar to ontogeny. In contrast, the reconstitution of CD4+CD8- T cells did not resemble ontogeny.
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PMID:Recovery of mononuclear cell subsets after bone marrow transplantation: overabundance of CD4+CD8+ dual-positive T cells reminiscent of ontogeny. 134 75


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