UMLS:C0019693 - FACTA Search

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

To study the pathogenesis of malignant lymphomas (ML) in intravenous drug-abuser HIV-infected patients, we analyzed 19 cases of reactive lymphadenopathy (LAS) and 10 cases of ML. Clonality and differences in characteristics of these lymphoproliferative disorders were investigated by immunohistochemical and Ig and TCR gene rearrangement analyses. Rearrangements at the c-myc locus and presence of HIV and EBV viral genomes were also investigated. Four out of the five non-Hodgkin's lymphomas (NHL) analyzed were high-grade extranodal ML and were found to derive from precursor B cells. Monoclonal cell expansions were also detected in 2 cases of LAS. These cell expansions also consisted of precursor B cells. HIV genome was not detected in any of the samples tested and was therefore considered not to be involved as an etiological agent in these lymphoproliferative disorders. EBV genome was present in a clonal episomal form in the five Hodgkin's disease (HD) specimens tested. This finding suggested that a clonal cell population harboring the EBV viral genome must be present in HDs, pointing to a possible etiological relationship between EBV and HD in HIV-infected patients.
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PMID:Pathogenesis of malignant lymphomas in intravenous drug-abuser, HIV-infected patients. 217 49

In H-2d mice, the immunodominant determinant of the HIV-1-IIIB gp160 envelope glycoprotein recognized by CD8+ CTL is represented by a 15-residue synthetic peptide (315-329: RIQRGPGRAFVTIGK). This peptide is seen in association with the Dd class I MHC molecule expressed on H-2k L cell fibroblast targets. We explored the structural requirements for CTL recognition of this peptide at the levels of both the peptide molecule and the class I MHC molecule. Using several transfectants expressing recombinant Dd/Ld molecules, we found that presentation of this epitope required both the alpha 1 and alpha 2 domains of the Dd molecule, in contrast to certain instances of allorecognition for which alpha 1 of Dd was sufficient in association with alpha 2 of Ld. Because this peptide derives from a hypervariable segment of the HIV envelope, substituted peptides could be used to define not only the structures affecting interaction of peptide with class I MHC molecule and with the TCR, but also the structural basis for the effect of naturally occurring viral variation on CTL recognition. The CTL-LINE specific for this HIV-1-IIIB-derived sequence could not recognize the HIV-1-RF variant-derived sequence from exactly the same site (315-329:--HIGPGRVIYATGQ). Peptides with single amino acid substitutions from the HIV-1-IIIB sequence toward the HIV-1-RF sequence were made to test the effect of each residue significantly affected recognition, and only one, 324(F), was obligatory. Moreover, both 322(R) and 324(F) substituted peptides failed to inhibit the binding of the wild type peptide to the MHC molecule. Therefore, the amino-acids 322(R) and 324(F) seem to be involved in regulating peptide interaction with the Dd class I MHC molecule. In contrast, 325(V) appeared to affect interaction with the TCR. We suggest that sequence variations among known HIV-1 isolates that affect peptide binding to MHC such as those described here, if occurring during the course of infection of an individual, could result in failure of the MHC molecules of that individual to present the peptide. If the number of dominant HIV CTL epitopes is indeed very limited, such a blind spot could allow the virus to escape immune control, proliferate rapidly, and cause AIDS.
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PMID:Structural requirements for class I MHC molecule-mediated antigen presentation and cytotoxic T cell recognition of an immunodominant determinant of the human immunodeficiency virus envelope protein. 247 5

The state of T cell activation and proliferation controls HIV-1 replication and gene expression. Previously, we demonstrated that the administration of PHA and PMA to the human T cell line Jurkat activates the HIV-1 enhancer, which is composed of two nuclear factor kappa B (NF kappa B) binding sites. Here, we show that PMA alone is sufficient for this effect. In addition, activation of T cells through the surface proteins TCR/CD3 and CD28 increased gene expression directed by the HIV-1 long terminal repeat (LTR) to the same extent as PMA. Analysis of 5' deletions in the LTR revealed that the NF kappa B binding sites and sequences in the upstream U3 region are required for this response. Whereas cyclosporin A did not inhibit the effect of PMA, it reduced the effects of agonists to TCR/CD3 and CD28 on the LTR. H7, an inhibitor of protein kinase C (PKC), blocked the effects of all stimuli. Thus, PMA activates the NF kappa B sites through a PKC-dependent pathway while ligands to TCR/CD3 and CD28 activate the LTR through a cyclosporin A-sensitive, PKC-dependent pathway of T cell activation. We conclude that mechanisms involved in the expression of IL-2 and the alpha-chain of the IL-2R alpha genes also play a role in the regulation of HIV-1. Physiologic stimuli can activate HIV-1 gene expression; agents that block T cell activation also inhibit activation of the LTR. These observations might serve as a model for the regulation of HIV-1 gene expression in peripheral blood T cells.
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PMID:Signaling through T lymphocyte surface proteins, TCR/CD3 and CD28, activates the HIV-1 long terminal repeat. 253 62

The present study was undertaken to determine whether human PBL can be specifically focused to lyse cells infected with HIV-1 by mAb heteroconjugates that can bridge target and effector cells. A mAb directed against the central portion of HIV-1 glycoprotein gp110 was chemically cross-linked to a mAb directed against the CD3/TCR complex or to a mAb directed against the CD16 Fc gamma-R expressed on large granular lymphocytes (LGL). HIV-1-infected cells, but not uninfected cells, were found to be lysed to a greater extent by PBL in the presence of the gp110 X CD3 or the gp110 X CD16 antibody heteroconjugate than in the presence of the single antibodies or a mixture of the mAb comprising the heteroconjugates. Pretreatment of PBL with anti-CD3 or IL-2 augments their ability to lyse HIV-1-infected cells in the presence of the heteroconjugates. Lysis by anti-CD3-activated PBL in the presence of the gp110 X CD3 heteroconjugate was found to be mediated by CD8+-enriched T cells, whereas lysis by IL-2-treated PBL in the presence of the gp110 X CD16 heteroconjugate is mediated by PBL enriched for CD16+ cells, which are primarily LGL. Furthermore, PBL from asymptomatic, HIV-1-infected seropositive donors were found to be functional in lysing HIV-1-infected cells in the presence of the antibody heteroconjugates. Such antibody heteroconjugates, which can target T cells or LGL to lyse HIV-1-infected cells, may be of prophylactic or therapeutic value in HIV-1-infected individuals.
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PMID:Lysis of cells infected with HIV-1 by human lymphocytes targeted with monoclonal antibody heteroconjugates. 296 25

Stimulation of human immunodeficiency virus type 1 (HIV-1)-infected donor peripheral blood mononuclear cells (PBMCs) via the TCR-CD3 complex induces HIV-1 production in vitro (Zarling JM, et al.: Nature [London] 1990;347:92; Haffar OK, et al.: J Virol 1992;66:4279; Moran PM, et al.: AIDS Res Hum Retroviruses 1993;9:455). However, in addition to the primary stimulatory signal delivered through the TCR-CD3 complex, optimal T cell activation requires secondary or costimulatory signals delivered via various T cell accessory proteins (Alton A, et al.: Adv Immunol 1990;48:227). In this article we explore the role of costimulation of T cells via CD28 in HIV-1 replication. Ligation of CD28 with either a CD28-specific MAb or by coculture of PBMCs with Chinese hamster ovary (CHO) cell lines stably expressing either of the CD28 counterreceptors, B7-1 (CD80) or B7-2 (CD86), concomitant with stimulation via CD3, results in increased virus replication compared to stimulation via CD3 alone. CD28 ligation also augments de novo infection of CD3-stimulated seronegative donor PBMCs with cell-free virus. Increased virus replication following CD28 ligation is not solely attributed to increased levels of endogenous IL-2, because addition of an anti-IL-2-neutralizing antibody only partially inhibits the response. In contrast, interfering with the interaction between CD28 and its counterreceptors on antigen-presenting cells (APCs) using CTLA4Ig effectively inhibits virus replication. At high concentrations CTLA4Ig also reduces cell proliferation. These in vitro results suggest that CD28 plays a central role in HIV-1 replication and that interfering with the CD28 costimulatory pathway may modify the course of HIV-1 infection.
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PMID:Costimulation of CD4+ T cells via CD28 modulates human immunodeficiency virus type 1 infection and replication in vitro. 749 35

Recent studies have identified genes involved in resistance to intracellular pathogens. Such genes include the murine MHC class I gene, Ld (toxoplasmosis), HLA-BW53, HLA DRB1* 1302-DQ B10s01 and TNF2 (malaria), murine Nramp (toxoplasmosis, leishmaniasis and tuberculosis), gene(s) modulating the T-helper type 1 and type 2 dichotomy (leishmaniasis, leprosy and HIV infection) and the natural killer cell complex (cytomegalovirus infection). There also have been other advances in immunogenetics that have led to a better understanding of resistance to intracellular pathogens. These include effector mechanisms of immune response genes and factors modulating genetic susceptibility. Identification of genes that determine resistance/susceptibility (and their effector mechanisms) has impacted on vaccine development. Immunogenetics has been important in characterizing roles of TCR genes, superantigens, and host genes that play a role in molecular mimicry in disease pathogenesis. In addition, recent work with gene knockout, recombinant inbred or congenic, mutant, consomic, and transgenic mice, positional cloning, mouse/human gene homologies to identify candidate human resistance genes, and the rapid expansion of the gene transcription maps of the human genome, have been important in analysis of resistance to intracellular pathogens.
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PMID:Immunogenetics in the analysis of resistance to intracellular pathogens. 749 19

The mucosal immune system of the female reproductive tract is of central importance for protection against sexually transmitted diseases, including HIV; however, this arm of the immune system remains poorly understood. Antiviral CTL responses never have been documented in the genital tract and the role of CTL in this anatomic site is unknown. In this study, CD8+ intraepithelial lymphocytes (IEL) in the vaginas of six simian immunodeficiency virus (SIV)-infected female rhesus macaques were identified by immunohistochemistry to be CD2+ and TCR beta-chain+. In addition, the majority of CD8+ IEL contained TIA-1+ cytoplasmic granules that are associated with CTL activity. CD8+ T cells were isolated from the vaginal epithelium and submucosa and amplified by limiting dilution in the presence of feeder cells. SIV p55gag and/or gp160env-specific lysis was detected in cultures of vaginal epithelial but not submucosal CD8+ T lymphocytes. Estimated SIV-specific precursor CTL frequencies were higher in the vaginal CD8+ IEL population of chronically infected monkeys than in the same cells from acutely infected monkeys or a naive control monkey. These results provide the first demonstration that antiviral CTL are present in the vaginal epithelium, and suggest that a vaccine may be able to generate anti-HIV CTL in the genital mucosa.
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PMID:Antiviral cytotoxic T lymphocytes in vaginal mucosa of simian immunodeficiency virus-infected rhesus macaques. 749 75

Peripheral blood mononuclear cells were quantified for the subsets of CD4, CD8, and CD19 lymphocytes by using CD45RA (2H4), CD29(4B4), CD57, CD5, CD10, Leu8, HLA-DR, and TCR gamma delta-1 monoclonal antibodies and dual color immunofluorescence. A comparative analysis of lymphocyte subpopulations was made among 52 HIV-infected and 50 age-matched control children and 30 HIV-seropositive and 27 negative control adults. A significant decrease in the CD4+CD45RA+ "naive" cells was much more marked in HIV-infected children than in HIV-infected adults. A significant percentage increase in the CD4+CD29+ "memory" cells was observed in HIV-infected children but not in infected adults; however, the absolute numbers were usually decreased in all age groups. The mean percentage and absolute numbers of CD4+CD7+ and CD4+Leu8+ cells were decreased in HIV-infected children, although usually not significantly. The CD3+TCR gamma delta-1+ did not show any change in the infected children tested. The mean percentage and absolute number of the CD8+HLA-DR+ cells increased significantly in HIV-infected persons of all ages. The CD8+CD57+ cells were increased in percentage and absolute number in HIV-infected children ages 1-4 and 4-8 years. In the adults, no change was noted in either the percentage or absolute number of CD19+CD5+ B cells, a finding similar to that noted in HIV-infected children above 1 year of age. Although adults showed a significant decrease in both percentage and numbers of CD5- B cells, an increase was noted in the 7- to 12-month-old HIV-infected children. The CD19+CD10+ cells showed a slight but significant decrease in the youngest age group and a significant increase in the older age groups of HIV-infected children. These findings indicate that several lymphocyte subpopulations are altered differentially during HIV infection in children of varying ages and in adults.
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PMID:Subpopulations of T and B cells in perinatally HIV-infected and noninfected age-matched children compared with those in adults. 751 Oct 82

HIV gp120 binding to CD4 suppresses TCR function. The molecular mechanism of this anergizing effect is incompletely understood. Studies reported here reveal that CD4 ligation initiates p56lck activation and renders human peripheral T cells and HPB-ALL cells hyporesponsive to Ag receptor stimulation, as indicated by the failure of TCR binding ligands to induce either protein tyrosine phosphorylation or elevation of intracellular-free calcium concentration. To approach the possibility that p56lck-mediated tyrosine phosphorylation of specific sites within TCR zeta-chain might be involved in the gp120-induced TCR signaling defect, we tested the kinase's ability to phosphorylate various zeta peptides. Kinetics analyses indicate that peptides derived from the in vitro autophosphorylation site of p56lck Y394 and two sites within zeta, Y84, and Y152, are equally effective substrates for p56lck, whereas p56fyn prefers a substrate peptide derived from a different site within zeta, Y142. Although these data are consistent with the possibility that gp120-mediated signal disruption of TCR could be due to p56lck phosphorylation of Y84 and Y152 residues within zeta, further experiments revealed that gp120 does not induce detectable zeta tyrosine phosphorylation under conditions in which it disrupts TCR signaling. These data indicate that gp120 can induce uncoupling of TCR from the earliest events in signal transduction and that this effect can be mediated by a mechanism other than tyrosine phosphorylation of TCR zeta-chain.
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PMID:gp120 ligation of CD4 induces p56lck activation and TCR desensitization independent of TCR tyrosine phosphorylation. 752 45

Several studies have suggested that activation-induced apoptosis of Ag-specific CD4+ T cells leads to depletion of this subset during HIV infection. The bacterial superantigen, staphylococcal enterotoxin A (SEA), is known to induce activation-induced apoptosis in the TCR V beta-bearing CD4+ T cells in the periphery after clonal expansion of these cells. The murine retroviral model of AIDS (MAIDS), which is induced by LP-BM5 murine leukemia virus, shares many common features with HIV infection in humans, except that CD4+ T cells increase progressively in susceptible strains. In this study, we challenged SEA to MAIDS mice and examined whether this retrovirus affects the fate of the SEA-reactive CD4+ T cells in vivo. At 4 wk post-infection with LP-BM5 murine leukemia virus, clonal expression and subsequent deletion of SEA-reactive CD4+V beta 3+ T cells occurred normally after SEA administration, whereas in vitro proliferative responses were severely impaired. At 8 wk postinfection, the in vivo expansion of CD4+V beta 3+ T cells was evident, but not followed by clonal deletion, as late as 14 days after SEA administration. This expanding subset in the infected mice expressed the Fas Ag in the same amount as the same subset in uninfected controls. These findings suggest that activation-induced apoptosis of superantigen-reactive CD4+ T cells is interfered with in vivo during the course of MAIDS, which is not attributable to underexpression of the Fas Ag by the CD4+ T cells.
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PMID:Clonal expansion but lack of subsequent clonal deletion of bacterial superantigen-reactive T cells in murine retroviral infection. 752 98

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