Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Identification of the components of protective immunity are crucial for the development of effective prophylactic and therapeutic vaccine strategies. Analysis of HIV-specific responses in exposed but uninfected individuals might thus provide a unique resource to elucidate the components and correlates of protective immunity to HIV. In the present study we analyzed HIV-specific cytotoxic and helper T lymphocyte responses in health care workers (HCW) exposed to body fluids from HIV-positive individuals. HCW exposed to blood from HIV-negative individuals as well as healthy donors served as controls. Cytotoxic T lymphocyte (CTL) responses to HIV envelope (env) peptides were detected in 7/20 (35%) HCW exposed to HIV-positive blood and in none of the 20 health care workers exposed to uninfected blood or the seven healthy blood donors studied. HIV-specific CTL responses were detected only after in vitro stimulation, and were MHC class I restricted. No MHC class I restriction elements were uniformly identified among the different responders. 21/28 (75%) HCW exposed to contaminated blood responded to env as measured by IL-2 production to the peptides, in contrast to only 9/38 (24%) HCW exposed to HIV seronegative blood and 3/35 (9%) healthy blood donors. All the HIV exposed individuals were seronegative on repeated ELISA tests, and no evidence of infection was obtained by PCR analysis. These findings indicate that a single exposure to HIV can induce CTL immunity to HIV antigens, in the absence of other evidence of infection.
 ...
PMID:ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids. 763 81

Muscle biopsies from 21 dermatomyositis (DM) and 7 polymyositis (PM) patients were studied by conventional histoenzymatic reactions and immunoreacted with antibodies against T cells and subsets, B cells, macrophages, activated T cells, proliferating cells, transferrin and IL-2 receptors, and natural killer cells. The expression of both class I and II molecules from the major histocompatibility complex (MHC) was also tested. As control groups we used muscle biopsies from normal healthy people, from chronic alcoholics and from a cohort of HIV-1 infected patients. In DM cases, severe muscle fiber necrosis, predominant perivascular infiltrates, fibrosis and perifascicular atrophy were the rule whereas in PM cases, endomysial infiltrates and the existence of partially invaded non-necrotic cells were more frequent. Perivascular B cells were found only in some DM cases. Transferrin and IL-2 receptors, proliferating cells and NK cells were detected in some cases from both diseases. MHC class I molecules were detected mainly in perifascicular fibres in DM while in PM the stronger expression was demonstrated in non-necrotic partially invaded cells, suggesting for the latter a MHC-restricted T-cell cytotoxicity. MHC Class II molecules expression in endothelial cells was detected in a variable fashion in both diseases, probably reflecting different stages of activation of such cells.
 ...
PMID:Idiopathic inflammatory myopathies. Immunohistochemical analysis of the major histocompatibility complex antigen expression, inflammatory infiltrate phenotype and activation cell markers. 767 62

Cytotoxic T cells are the main antigen-specific effector cells of the cellular immune system and MHC class I restricted cytotoxic T-lymphocyte (CTL) responses in mice, acting against the HIV-1 envelope protein, are known to be predominantly directed against an amino acid sequence in the third hypervariable domain. We have investigated the epitope specificity of anti-HIV-1 CTL in healthy human volunteers inoculated with a recombinant vaccinia expressing the HIV-1 gp160 envelope gene. Their isolated lymphocytes were stimulated in vitro with autologous HIV-1 infected cells. Our results show that immunization with recombinant virus is able to generate virus-specific CTLs to the HIV-1 gp160 envelope protein and to a 15-residue synthetic peptide corresponding to a highly variable region of the envelope p18(IIIB). The CTL response was restricted by class I MHC molecules HLA-A2 and A3 that commonly occur in the human population.
 ...
PMID:Envelope protein and p18(IIIB) peptide recognized by cytotoxic T lymphocytes from humans immunized with human immunodeficiency virus envelope. 768 70

In view of the importance of cell-associated virus in AIDS virus transmission, an HIV vaccine should be able to induce a virus-specific CTL response. Traditional subunit vaccines have not elicited virus-specific CD8+ MHC class I-restricted CTL. We have used the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model to explore the use of CTL epitope peptide-helper peptide conjugates for the vaccine elicitation of AIDS virus-specific CTL. We found that both the CTL epitope peptide-helper peptide conjugate and the CTL epitope peptide alone, when delivered in an emulsion with IFA, induced CTL epitope-specific CD8+ MHC class I-restricted CTL. These effector cells recognized processed viral protein and were readily cloned from PBL of the immunized monkeys. Moreover, the cloned effector cells inhibited SIVmac replication in PBL. Immunization with the CTL epitope peptide used in this study also elicited a CD4+ PBL proliferative response, suggesting that the peptide also contained a helper epitope. These studies provide further evidence for the potential usefulness of peptide-based AIDS virus vaccines.
 ...
PMID:Synthetic peptide in mineral oil adjuvant elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes in rhesus monkeys. 769 65

We have previously reported the induction of MHC class I-restricted, CD8+ cytotoxic T lymphocytes (CTLs) specific to human immunodeficiency virus type 1 (HIV-1) in mice by a 15-amino acid peptide (R15K) from the V3 loop in gp120. We now present evidence showing that CTL activity induced by R15K was stable for 8-10 weeks after a single injection and that as little as 20 micrograms peptide was sufficient for efficient CTL induction in vivo. While induction of CTLs was efficient with R15K emulsified in either complete or incomplete Freund's adjuvant, only a low-level CTL response was observed in mice immunized with R15K in either alum or saline. We analyzed a series of carrier-free synthetic peptides ranging in length from 8 to 24 amino acids from the V3 loop region and observed that peptide R10I consisting of 10 amino acids from the middle portion of R15K was more efficient for CTL induction. Additionally, lymph node cells from mice immunized with 24 and 15 amino acid peptides (N24G and R15K, respectively) when restimulated in vitro with R10I exhibited greater HIV-1 env-specific CTL activity than when either of the longer peptides was used for restimulation. A peptide consisting of only 8 amino acids (R8K) was sufficient neither for inducing primary CTLs nor for in vitro restimulation of lymph node CTL precursors. These results establish that a carrier-free 10-amino acid synthetic peptide from the V3 loop region in HIV-1 gp120 has the optimal sequence for efficient induction of HIV env-specific CTLs in mice.
 ...
PMID:Studies on in vivo induction of HIV-1 envelope-specific cytotoxic T lymphocytes by synthetic peptides from the V3 loop region of HIV-1 IIIB gp 120. 772 83

Because of the importance of the envelope glycoprotein (Env) in determining the pathogenicity of HIV-1 and the importance of the immune response to Env in controlling virus spread, attempts are being made to study HIV-1 Env-directed immunity in primate models. To date HIV-1 Env-specific effector T lymphocyte responses have not been demonstrated in virus-infected nonhuman primates. We have previously reported that cynomolgus monkeys can develop a persistent infection with a chimeric simian-human immunodeficiency virus (SHIV) composed of SIVmac239 carrying the HIV-1 env, tat, rev, and vpu genes. We now demonstrate that SHIV-infection of another macaque species, the rhesus monkey, generates persistent, HIV-1 Env-specific cytolytic T lymphocyte (CTL) responses. These CTL are CD8+ and major histocompatibility complex (MHC) class I-restricted. The induction of CTL was correlated neither to the virus load nor to the MHC class I haplotypes of the monkeys. The SHIV-infected rhesus monkey can, therefore, now be employed for studying effector T lymphocyte recognition of HIV-1 Env.
 ...
PMID:Human immunodeficiency virus type 1 envelope glycoprotein-specific cytotoxic T lymphocytes in simian-human immunodeficiency virus-infected rhesus monkeys. 774 49

We have developed a unique multiple step procedure to inactivate human immunodeficiency virus chemically with a very high safety margin while retaining antigenically active structural virion proteins, including gp120, in the final immunogen. The whole virus preparation (1-10 micrograms per dose) was highly immunogenic in a variety of small mammals and induced antibodies that recognized homologous and heterologous strains of HIV-1. Sera from immunized animals bound to peptides representing the entire sequence of the external glycoprotein gp120. Neutralizing antibodies active against the homologous immunizing strain and against heterologous HIV-1 strains were also elicited. Sera with virus neutralizing activity did not bind to MHC class I proteins derived from the human cell line used to grow the virus.
 ...
PMID:An experimental chemically inactivated HIV-1 vaccine induces antibodies that neutralize homologous and heterologous viruses. 776 78

T cells can recognize the antigen only if it is associated with self MHC molecules on the surface of antigen presenting cells (APC). There are several characteristic parameters defining interaction of MHC molecule with antigenic peptides giving circumstances for specific antigen presentation and an individualized immune response. Here are assessed some size and conformational parameters of the peptides presented by MHC class I molecules-lengths, widths, van der Waals volumes and surfaces-using COSMIC 2.0 software. The peptides derived from HIV gp 160 are obtained from literature and are known to be active and inactive in a cytotoxicity assay. An increased tendency for beta- or beta-like structures and volumes close to those of the MHC binding site are encountered in the case of active peptides.
 ...
PMID:Molecular aspects concerning antigen oligopeptide selection by MHC class I molecules. 782 64

The ability to induce a strong, HIV-1-specific CD8+ CTL response is assumed to be an important component of a protective HIV-1 vaccine. Identification of CTL responses in seronegative vaccines requires in vitro stimulation of CTL precursors with cells that have processed HIV-1 gene products via the endogenous intracellular pathway for presentation in association with MHC class I molecules. We have developed a method to detect CTL responses to HIV epitopes and HIV-infected cells that can be applied to recipients of HIV vaccines regardless of immunization with a particular recombinant virus or prior immunological status. Primed CTL precursors from PBMCs are stimulated for two 1-week cycles with autologous monocyte-derived macrophages infected with HIV-1Ba-L. The effector CTLs generated in culture are then tested in a standard chromium release assay for lysis, using autologous target cells, including EBV-transformed lymphoblastoid cell lines (LCLs) expressing individual HIV-1 proteins following infection with a recombinant vaccinia virus, or LCLs transduced with the CD4 gene and infected with isolates of HIV. Using this methodology we have examined CTL responses induced by candidate HIV vaccines in HIV-1-uninfected individuals participating in phase I/II AVEG trials. Our findings indicate that this approach makes it possible to overcome some of the previous technical difficulties involved in the analysis of CTL responses in immunocompetent vaccine recipients and thereby facilitates the identification of potentially effective candidate HIV-1 vaccines.
 ...
PMID:Evaluation of cytotoxic T cell responses to candidate HIV-1 vaccines in HIV-1-uninfected individuals. 786 36

The immune response of peripheral blood lymphocytes (PBL) of non-exposed human individuals to the Nef protein of HIV-1 was studied. Nef is a regulatory protein of HIV which is immediately expressed after infection and which seems to be important in the pathogenicity of HIV. Nef may therefore serve as a potential target for effective immunity against HIV infection. Epstein-Barr (EBV)-transformed lymphoblastoid B cell lines (LCL) were established from four healthy young seronegative adults and transfected with the Nef gene. These cells served as stimulator cells for autologous PBL in vitro and as target cells for CTL. CTL responses were readily generated against Nef-transfected LCL, consisting of Nef-specific and putative EBV-specific CTL. Nef-specific CTL were generated exclusively from CD8+ cells and were MHC class I restricted. Since a vigorous Nef-specific CTL response in non-infected individuals was unexpected, CTL precursor frequencies were determined by limiting dilution analyses in non-fractionated PBL and in PBL separated into the CD45RO- (naive) and CD45RO+ (memory) T cell populations. As expected, the putative EBV-specific CTL precursors were predominantly found in the CD45RO+ subset at frequencies typical for memory T cells. Nef-specific CTL precursors, in contrast, were found predominantly in the CD45RO- population, at even higher frequencies of approximately 1/1000-1/3000. Nef may thus display either an unusually high number of immunogenic peptides or a limited number of peptides presented in a very efficient way, so that many T cells including low affinity cells, would be triggered.
 ...
PMID:Human immune response to HIV-1-Nef. I. CD45RO- T lymphocytes of non-infected donors contain cytotoxic T lymphocyte precursors at high frequency. 786 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>