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

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

We previously demonstrated that long term treatment of the Ag-specific CD4+ T cell clone P28D with soluble HIV envelope glycoprotein gp120 results in a marked impairment of CD3/TCR-mediated responses. In this report, to further understand these inhibitory effects, the binding properties and internalization of gp120 have been investigated, in parallel with functional studies, in long term incubations of P28D cells with gp120. Immunofluorescence studies show that surface-bound gp120 level is maximal within 1 h of incubation at 37 degrees C and then gradually decreases. This decrease is accompanied by a progressive down-modulation of membrane CD4 (30-35% loss over a 18-h incubation period) without concomitant alteration of the CD4 mRNA steady-state level. Similar experiments performed with 125I-labeled gp120 demonstrate that the glycoprotein is progressively internalized (up to 35% internalized material after 18 h) and that it accumulates inside the cells. Confocal microscopy studies show that internalized gp120 is concentrated in localized intracellular compartments. CD4 also accumulates in compartments with a similar localization and is stained with mAb OKT4 but not with mAb OKT4a. Concomitantly to internalization of gp120 and disappearance of membrane CD4, a correlated loss of the CD4-associated tyrosine kinase p56lck is evidenced. Interestingly, a progressive impairment of the P28D responses to specific Ag or to anti-CD3 mAb is also observed. Inhibitions of T cell proliferation increase with the degree of both CD4 and p56lck down-modulation. Removal of exogenous gp120 results in a rapid and spontaneous release of internalized gp120 into a degraded form. A progressive restoration of CD4 and p56lck levels is also noticed. In parallel, CD3/TCR-mediated responses of clone P28D are fully recovered. Altogether, our results suggest that HIV-1 glycoprotein gp120 is able to down-modulate membrane CD4 presumably by a cointernalization process and to further down-modulate the associated p56lck. This dual phenomenon is presumably involved in the direct immunosuppressive effect of gp120 on the CD3/TCR-mediated activation pathway.
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PMID:Internalization of HIV glycoprotein gp120 is associated with down-modulation of membrane CD4 and p56lck together with impairment of T cell activation. 153 86

Immunophenotyping of different lymphocyte populations was carried out in parallel on 113 consecutively received specimens of human peripheral blood using 2 different data acquisition and analysis systems (EPICS C and 4Cyte-Acmecyte) on the same flow cytometer (EPICS C). The phenotypes analyzed were CD3+, CD4+, CD8+ CD56+ CD16+ CD3-, TCR-gamma delta+ CD8-, and TCR-gamma delta+ CD8+. Both HIV- and HIV+ specimens were used for this study, including some with CD4 levels as low as 2% of all lymphocytes. Despite differences in gating procedures and shapes of bitmap (rectilinear vs. "amorphous"), the 2 methods agreed to within 2% positive cells in 97% of the cases. Although some statistically significant biases in the methods were observed, these were small and not biologically important. We conclude that both methods of data acquisition and analysis, as employed by experienced operators on the EPICS C flow cytometer, gave essentially equivalent results for lymphocyte sub-populations in peripheral blood preparations.
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PMID:Comparison of lymphocyte immunophenotypes obtained simultaneously from two different data acquisition and analysis systems on the same flow cytometer. 154 69

It has been previously demonstrated that the HIV envelope glycoprotein gp160 can inhibit the activation of T cells triggered by phytohemagglutinin, anti-CD3 antibody and Ag, caused in part by the modulation of the expression of CD4. In this study, we show that gp160 is also able to inhibit the Ag-independent adhesion of CD4+ T cells to B cells as anti-CD4 antibodies do. In addition, synthetic peptides (14 to 21 mer) derived from the gp160 sequence and analogous to the putative binding site of gp160 to CD4 (residues 418-460), and also covering residues 460 to 474 inhibit the capacity of both CD4+ T cell proliferation induced by tuberculin and anti-CD3 antibody and adhesion. This was not associated with inhibition of Ca2+ flux in T cell activation. These inhibitory activities are specific because a) CD4+ T cells but not CD8+ T cells are susceptible to their effects, and b) soluble CD4 neutralizes the inhibitory activities. Peptides are, however, about 100- to 1000-fold less potent inhibitors than the native gp160. In addition, they do not induce CD4 modulation. It is thought therefore that at least part of the gp160 inhibitory activity is not secondary to CD4 modulation but may rely either upon steric hindrance of CD4-MHC class II interaction, of CD4/CD3 TCR complex interaction, or upon negative signaling through binding to CD4. The latter hypothesis is suggested by the inhibition by gp160, gp160-derived peptides, and anti-CD4 antibodies of the Ag-independent adhesion of CD4+ T cells. This adhesion process has been previously shown to be mediated by the LFA-1 and CD2 molecules and not by the TCR/CD3 complex and by CD4. Together, these results support the role of part of the 418-460 region of gp160 as a binding site to CD4, and suggest that binding of part of this region to CD4 can alter T cell proliferation and adhesion. It is proposed that these effects are mainly mediated by negative signaling through CD4.
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PMID:Inhibition of CD4+ T cell activation and adhesion by peptides derived from the gp160. 167 23

Like particular monoclonal antibodies to CD4, monoclonal antibodies to epitopes localized at the top of the alpha-subunit (CD11a) and at the stem of the beta-subunit (CD18) of the lymphocyte function associated antigen-1 (LFA-1) block syncytium formation when added to CD4+ T-cells before or shortly after (5 min) cell free HIV-1 is added. This indicates involvement of LFA-1 epitopes in the early stage of cell-free infection. Syncytium formation is still blocked by CD4 antibodies when added two hours after virus adsorption, CD11a and CD18 antibodies are ineffective at this late stage. Radio-immune precipitation experiments in acutely infected T-cells with the appropriate CD11a and CD18 antibodies suggested a link between CD18 and CD4 in the cell lines studied, possibly mediated by the CD3/TCR complex. In chronically infected cells, where little CD4 is expressed, LFA-1 antibodies still precipitate the viral envelope, pointing to a direct LFA-1 envelope interaction in that late stage of infection. Our results indicate that a limited number of LFA-1 epitopes is involved in syncytium formation among T-cells, none of which is required for virus entry in the cell or virus spread in the culture.
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PMID:CD11a/CD18 (LFA-1) epitopes involved in syncytium formation among CD4+ T-cells following cell free HIV-1 infection. 170 84

The transcription factor NF-kappa B has been implicated in the mitogen-induced expression of several genes that are critical for the immunologic function of T cells such as those encoding IL-2 and the IL-2R alpha chain (IL-2R alpha). We show here that NF-kappa B is induced in T cells activated by Ag, anti-CD3 antibody, or allogeneic stimulation. The induction of NF-kappa B via the TCR was dependent on protein kinase C. IL-2, which also activates IL-2R alpha expression and proliferation in T cells, was not able to induce NF-kappa B. TCR-mediated induction of NF-kappa B suggests a central role for this factor in activated T cells and also provides a mechanism for activation of latent HIV provirus during the normal immune response.
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PMID:Physiologic activation of T cells via the T cell receptor induces NF-kappa B. 183 61

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

This study describes the inhibitory effect exerted by activated CD8+ T cells on the replication of HIV in naturally infected CD4+ T cells. Highly purified CD4+ T cells from asymptomatic HIV seropositive individuals were stimulated with anti-TCR mAb-coated beads in the presence of IL-2. HIV was subsequently reproducibly isolated in cell supernatants from all study participants (53 cultures from 42 individuals). Both autologous and allogeneic CD8+ T cells from asymptomatic HIV seropositive and healthy HIV seronegative individuals inhibited the replication of HIV in these cultures in a dose-dependent manner. CD8+ T cells from patients with AIDS showed reduced or no such inhibitory activity. The inhibitory effect was not dependent on direct cell-cell contact: an inhibitory effect was exerted by CD8+ T cells across a semipermeable membrane, and an inhibitory activity was also exerted by the cell-free supernatants from activated CD8+ T cells. These results suggest that activated CD8+ T cells secrete a soluble inhibitor of HIV replication.
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PMID:CD8+ T cells inhibit HIV replication in naturally infected CD4+ T cells. Evidence for a soluble inhibitor. 196 79

It has been suggested that autoimmune phenomena contribute to the depletion of CD4+ T cells and the development of AIDS in HIV-1 infected humans based, in part, on observations that some HIV-1-infected humans have autoantibodies reactive with Ag expressed on uninfected CD4+ cells. In this study, 11 of 14 asymptomatic HIV-1-infected homosexuals and hemophiliacs, but none of 17 uninfected homosexuals or heterosexuals, were found to have cytotoxic lymphocytes in blood that can lyse uninfected CD4+ T cells from humans and chimpanzees but not human B lymphoblastoid cells or mouse T cells. The cytotoxic PBL were concluded to be CTL rather than NK cells, with the phenotype being CD3+, TCR-1 alpha beta+, CD8+, CD4-, CD16- based on findings that PBL-mediated lysis of uninfected CD4+ cells was 1) blocked by a mAb to CD3, which inhibits CTL but not NK activity; 2) diminished by treatment of PBL with a mAb to CD8 and C, but not by treatment with mAb to CD4 or CD16 and C; and 3) blocked by mAb WT31 directed against the TCR-1 alpha beta. In contrast, PBL from HIV-1-infected chimpanzees, which to date have not developed AIDS, lacked detectable CTL lytic for uninfected CD4+ cells.
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PMID:HIV-infected humans, but not chimpanzees, have circulating cytotoxic T lymphocytes that lyse uninfected CD4+ cells. 196 80

The immune deficiency induced by HIV has its origin in the interaction of the outer envelope glycoprotein gp120/gp41 with receptors present on human immunocytes. Virus binding to cells, virus entry and subsequent compartmentalization resulting in productive infection depends on the interaction of gp120/gp41 with CD4 and other accessory molecules. Gp120 and HIV are markedly immunosuppressive of T-cell responses and, in addition, HIV can functionally delete antigen responsiveness of T cells. Abolition of CD4 binding, by denaturation of gp120, allows study of T-cell epitopes in gp120 and shows the denatured molecule is highly immunogenic even in naive subjects (F. Manca, unpublished). The gp120-binding site of CD4 is shared with MHC class II molecules and the reaction of antibodies within this region of CD4 induces conformational changes that may be significant for virus entry into cells or for syncytial formation. The HIV envelope contains sites of sequence homology with monomorphic human MHC class II sites that do not appear to be naturally immunogenic in humans. In addition to the properties of gp120, it is hypothesized that HIV envelope may also represent an 'alloepitope' of class II to the human T-cell repertoire, and is therefore able to induce a chronic allogeneic response not dissimilar to experimentally induced GVHD. These features are of potential importance both for primary vaccination against HIV, and for the long-term treatment of HIV seropositive patients. Induction of effective T-cell responses to gp120 require use of a denatured or otherwise modified product lacking CD4-binding capacity. The potential distortion of the TCR repertoire by the class-II-homologous and CD4-interactive sequences must be assessed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:AIDS pathogenesis: HIV envelope and its interaction with cell proteins. 187 30


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