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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Fab' fragment of a monoclonal antibody (mAb) directed to CD3 (a portion of the T cell receptor) and the Fab' or F(ab')2 fragment of an mAb to HIV were combined to generate bifunctional antibody (BFA) consisting of antiCD3-Fab' conjugated with anti-HIV-Fab' (Fab'/Fab') or antiCD3-Fab' conjugated with anti-HIV-F(ab')2 (Fab'/F(ab')2), respectively. In the presence of these BFA, HIV-infected target cells were cytolysed by peripheral blood lymphocytes. Treatment of lymphocytes with Fab'/F(ab')2 type BFA rendered the lymphocytes significantly cytotoxic to HIV-infected target cells. Since BFA-armed lymphocytes can react on HIV-infected cells regardless of histocompatibility, lymphocytes from healthy donors could be armed with BFA for treatment of HIV-infected patients including those who do not exhibit histocompatibility with the lymphocyte donor.
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PMID:Specific cytolysis of HIV-infected cells by lymphocytes armed with bifunctional antibodies. 153 63

Previous studies revealed that antisense oligodeoxynucleotides to specific regions of the human immunodeficiency virus-1 (HIV-1) are potent inhibitors of replication of HIV-1 in vitro (Zamecnik, P. C., Goodchild, J., Taguchi, Y., and Sarin, P. S. (1986) Proc. Natl. Acad. Sci. U. S. A. 83, 4143-4146). We now report that antisense RNA, synthesized in vitro using T7 and SP6 RNA polymerase, displayed an anti-HIV-1 effect in the HTLV-IIIB/H9 system in vitro. Treatment of HIV-1-infected H9 cells with viral env region antisense RNA encapsulated in liposomes targeted by antibodies specific for the T cell receptor molecule CD3 almost completely inhibited HIV-1 production. The viral env segment covered a part of exon II of HIV-1 tat gene. No anti-HIV activity could be detected with similarly targeted liposome-encapsulated sense env RNA or with pol RNA synthesized in either the sense or antisense orientations, or with env region antisense RNA free in solution, or encapsulated in liposomes in the absence of the targeting antibody. A semiquantitative evaluation revealed that 4000-7000 RNA molecules became cell-bound in targeted liposomes; the half-life of the intracellularly present hybridizable antisense env RNA was approximately 12 h. Western blots showed that antisense env RNA suppressed tat gene expression by approximately 90% and gp160 production by 100%. These data were confirmed by immunoprecipitation studies. Northern blots (using an env probe) demonstrated the existence of all major HIV RNA species (9.3-, 4.3-, and 2.0-kb mRNA) in HIV-infected cells treated with antisense env RNA although at a reduced level. We conclude that the antisense env RNA inhibited viral protein production at the translational level.
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PMID:Inhibition of expression of human immunodeficiency virus-1 in vitro by antibody-targeted liposomes containing antisense RNA to the env region. 169 56

When antigen-specific T cells are pulsed by antigen-presenting cells (APC) in the presence of HIV they are functionally deleted following subsequent exposure to syngeneic APC in the absence of HIV. Recombinant soluble HIV envelope (gp120) is able to induce a similar effect which, unlike that induced by HIV, is reversible. Neither HIV nor gp120 affect the ability to respond to IL-2. Thus it is only antigen-specific responses involving the T cell receptor pathways and CD4/MHC class II interaction that appear to be inhibited by HIV-1 and gp120. Furthermore, the functional impairment caused by HIV-1 is specific to the T cells that respond to the antigen in co-culture with HIV, as there is no apparent effect on 'bystander'-activated T cells specific for another antigen. Antigen-specific T cell lines may be deleted by a signalling mechanism which involves molecules other than gp120/CD4 but still requires MHC class II restriction.
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PMID:HIV-induced deletion of antigen-specific T cell function is MHC restricted. 173 29

We have previously shown that HIV-1 seropositivity is associated with an increase in the difference between the number of CD3+ lymphocytes and the total number of CD4+ and CD8+ lymphocytes [CD3 - (CD4 + CD8)] among peripheral blood lymphocytes (PBL). To investigate the cellular basis of this increase, PBL from seronegative (SN) and AIDS-free seropositive (SP) homosexual men and intravenous drug users were analyzed by two-color flow cytometry. Results showed that SP compared to SN manifested the expected elevation in calculated [CD3 - (CD4 + CD8)] cells (87 vs 28 cells/mm3; P less than 0.001). Only small differences in lymphocyte populations that could contribute to this increase were observed, namely lymphocytes expressing the CD3+CD4-CD8-phenotype (67 vs 56 cells/mm3; P greater than 0.10) or the CD8dim phenotype (135 vs 142 cells/mm3; P greater than 0.10). However, SP had significantly lower numbers of cells expressing the CD56+CD3- phenotype characteristic of natural killer cells (81 vs 170 cells/mm3; P less than 0.001) and significantly higher numbers of T cells expressing the gamma delta T cell receptor (TCR) (81 vs 62 cells/mm3; P = 0.10). The latter difference was primarily due to higher numbers of cells coexpressing gamma delta-TCR and low levels of CD8 (27 vs 15 cells/mm3; P = 0.009). These data suggest that HIV-1 seropositivity is associated with low numbers of natural killer cells and high numbers of CD8+ gamma delta-TCR lymphocytes. Changes in these populations may reflect altered host defense against HIV-1 or altered T cell kinetics in the presence of HIV-1 infection.
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PMID:Flow cytometric analysis of gamma delta T cells and natural killer cells in HIV-1 infection. 182 68

The gamma delta T cell receptor (TcR) lymphocytes constitute 3-10% of human peripheral blood lymphocytes. Only a very small fraction of these cells is recognized by the delta TCS1 monoclonal antibody, directed against the V delta 1 chain of the receptor. We describe the immunological, virological and clinical data of a small group of seropositive subjects having high levels of gamma delta TcR T cells in the peripheral blood. Our flow cytometric studies show that most of these cells belong to the delta TCS1+ (V delta 1+), CD8 +/- (dim staining) subset. Patients with high gamma delta TcR T cell numbers were not characterized by the presence of an acute (IgM positive) or reactivated (as defined by high IgG titres against early antigen or IgA titres against viral capsidic antigen) Epstein-Barr virus infection. Cytomegalovirus infection was excluded by serological assays, and other herpes viral infections were not found after clinical examination. HIV p24 antigenaemia was present in two out of 11 subjects. AIDS patients had very high percentages of gamma delta TcR T cells. Altogether these data show that the selective expansion of delta TCS1+ cells in HIV1 seropositive subjects is not related to some exogenous antigen stimulation, but may be related to peculiar pathologic processes involving the immune system.
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PMID:A subset of gamma delta lymphocytes is increased during HIV-1 infection. 182 86

We have previously described an in vitro model for studying human immunodeficiency virus, type 1 (HIV-1) infection in CD4+ T cells [1]. This model employs the WE17/10 cell line, which loses expression of its T cell receptor/CD3 (TCR/CD3) after several months of productive infection. We have used this model to analyze the synthesis and posttranslational modification of viral and cellular proteins after HIV-1 infection and to determine the relationship of these changes to TCR/CD3 expression. Mainly we observe positive changes in protein expression after infection. A phosphoprotein, referred to as WH:1, appears in infected cells that still express their TCR/CD3 complex, and its persistence is linked to the presence of the complex. We examined whether loss of the TCR/CD3 complex could be associated with alterations in the T cell activation pathway as a result of infection. We used T cell activators and inhibitors to determine whether there were common elements between the two events. Quantitative enhancement in one spot, Cs:1, occurred after both Cyclosporin A treatment of uninfected cells and HIV-1 infection of untreated cells. Taken altogether, these data suggest that a correlation exists between negative regulation of late events in the T cell activation pathway and down regulation of the TCR/CD3 complex after HIV-1 infection.
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PMID:A comparative analysis of alterations in protein expression after activation or human immunodeficiency virus, type 1 infection of human CD4+ T cells. 191 47

Recently we described an HLA B27-restricted peptide derived from HIV gag p24 protein. In this study we have isolated an HLA B27-restricted peptide from the nucleoprotein (NP) of influenza A virus. The shortest fragment recognized by cytotoxic T lymphocyte (CTL) is eight amino acids long, residues 384-391. Comparison of the sequence of these two HLA B27 restricted peptides reveals homologies which can be aligned from one peptide to the other. Of the eight residues, two are identical: tryptophan and isoleucine. Both peptides have a positively charged residue at the N terminus, lysine at position 265 of gag and arginine at position 384 of NP. Using modified peptides we have shown that lysine or arginine is crucial for the interaction with HLA B27. The wild-type gag peptide blocked CTL recognition of NP peptide by influenza-specific CTL, but removal of the lysine prevented inhibition of NP peptide recognition. The importance of these charged residues was confirmed by the observation that truncated NP and gag peptides where the lysine or arginine was removed were not recognized by specific CTL. Further studies showed that the tryptophan residue influenced the association of the gag peptide with HLA B27, because the affinity of the gag peptide for B27 was strongly increased after replacing this residue with a leucine or a tyrosine. However, these peptides were not recognized by gag-specific CTL, suggesting that the tryptophan may interact with both HLA B27 and T cell receptor. These observations should help in the identification of HLA B27-restricted peptides from other viruses or organisms.
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PMID:Structural homologies between two HLA B27-restricted peptides suggest residues important for interaction with HLA B27. 212 95

The role of the CD4 molecule in the transmission and regulation of the biochemical signals involved in T cell activation was investigated using an anti-CD4 monoclonal antibody termed 6B10. 6B10 immunoprecipitated the 55-kDa CD4 molecule and detected an epitope of CD4 that overlapped with that detected by OKT4A, B, and D. 6B10, 6B10 Fab fragments and recombinant HIV envelope glycoprotein (gp120) induced calcium mobilization in PBMC. 6B10 stimulation also resulted in calcium mobilization in murine L cells expressing transfected CD4 gene products, indicating that CD4-mediated calcium mobilization occurred independently of the CD3/T cell receptor (TCR) complex. 6B10 induced a phosphatidylinositol response, but the response resulted in reduced inositol phosphate production compared to levels obtained using OKT3. Though 6B10 caused calcium mobilization and a phosphatidylinositol response, 6B10 did not induce DNA synthesis. The amount of inositol phosphates produced by 6B10 may be below the threshold necessary for cell cycle progression. We hypothesized that 6B10-mediated calcium mobilization is important in the regulation of T cell proliferation. 6B10, but not 6B10 Fab fragments, inhibited OKT3-induced DNA synthesis. Furthermore, 6B10 but not 6B10 Fab fragments inhibited OKT3-induced calcium mobilization, suggesting that crosslinking of CD4 may be an important factor determining whether signals result in both the up- and down-regulation of CD3/TCR complex function. The implication of this work is that signals generated via the CD4 molecule are important in the regulation of T cell function and that the signals generated as a result of HIV gp120 binding to CD4 can contribute to the mechanism by which HIV inhibits T cell function.
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PMID:The CD4 molecule transmits biochemical information important in the regulation of T lymphocyte activity. 213 31

To investigate the effects of persistant human immunodeficiency virus (HIV) infection on T cell reactivity, functional properties of peripheral blood T cells from HIV-seropositive homosexual men in various stages of infection were studied. T cell activation via CD3 resulting in proliferation and differentiation was measured in a model system independent of accessory cells, using immobilized anti-CD3 monoclonal antibodies (mAb). T cells from HIV-infected asymptomatic men had a decreased proliferative response compared to HIV-negative controls. T cells from AIDS-related complex (ARC) and AIDS patients, compared to T cells from asymptomatic HIV-infected men, had a significantly lower proliferative response to anti-CD3 mAb. This diminished response to anti-CD3 mAb was shown to be due to decreased interleukin (IL) 2 production and could be enhanced by co-stimulation with anti-CD28 mAb or by adding IL 2. Anti-CD3-induced generation of cytotoxic T lymphocytes was fully intact in early infection but was severely decreased in T cells from ARC and AIDS patients. Cytotoxic activity could be restored to near normal levels after co-stimulation with either anti-CD28 mAb or IL 2. Our data demonstrate a differential loss of T cell functions in the course of HIV infection which is predominantly caused by a lack of IL 2 production after stimulation via the CD3/T cell receptor complex. In early HIV infection this seems to be predominantly caused by a specific loss of memory T cells. However, in later stages of infection when both naive and memory T cell subsets are depleted, resulting in a normal naive/memory T cell ratio, T cell functions further deteriorate probably due to intrinsic activation defects. These findings may be of pathogenic relevance since diminished T cell reactivity may facilitate spreading and replication of virulent HIV variants heralding development of ARC and AIDS.
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PMID:Selective loss of T cell functions in different stages of HIV infection. Early loss of anti-CD3-induced T cell proliferation followed by decreased anti-CD3-induced cytotoxic T lymphocyte generation in AIDS-related complex and AIDS. 216 75

To characterize the cytotoxic events taking place in the lung of patients with HIV-1 infection, we studied the cells recovered from the bronchoalveolar lavage (BAL) of nine patients with AIDS, seven patients with AIDS-related complex, and two patients with lymphadenopathy. Phenotypic analysis was coupled to a series of functional evaluations of nonspecific cytotoxic abilities performed on lung effectors, including their property to bind K-562 targets, to release natural killer cytotoxic factor (NKCF), and to become cytotoxic following in vitro activation with rIL-2. Our results demonstrated that lung cells bearing the NK-related CD16, CD56, and CD57 antigens were quantitatively increased, irrespective of the disease stage. The majority of the cells also coexpressed the CD3 molecule and the alpha/beta T cell receptor (TCR), notably the phenotype characterizing MHC-unrestricted cytotoxic T cells. From a functional point of view, a severe impairment of the spontaneous cytotoxic ability was demonstrated in most patients. Evaluation at the single cell level showed a normal percentage of the effector/target conjugates formed by HIV-1 lymphocytes. The release of NKCF was undetectable in patients with AIDS even following lectin stimulation, whereas BAL cells from patients with earlier infection produced and/or could be triggered to release discrete amounts of NKCF by incubation with PHA. Studies designed to activate lung cytotoxic cells with rIL-2 showed that in most patients the stimulation of effector cells with rIL-2 enhanced the spontaneous killing and elicited a lymphokine-activated killer (LAK) phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxic events taking place in the lung of patients with HIV-1 infection. Evidence of an intrinsic defect of the major histocompatibility complex-unrestricted killing partially restored by the incubation with rIL-2. 238 2


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