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

Interleukin-2 (IL-2) plays an essential role in the clonal expansion of antigen-activated T lymphocytes (T cells). In fact, the expression of both IL-2 and IL-2 receptor (IL-2R, p55, CD25) genes is transiently induced upon T cell activation through the interaction of antigen/major histocompatibility complex (MHC) and T cell receptor complex. To elucidate the mechanism(s) of the induced gene expression for IL-2 and IL-2R, we have investigated for the presence of potential transcription factors that specifically interact with regulatory cis-elements. Here, we demonstrate that one such factor mediates the induced expression of both genes. Interestingly, the recognition sequences by this factor are significantly diverse in these two genes and are related to those of immunoglobulin (Ig) kappa chain and MHC class I genes. We provide evidence that this factor indeed binds to the IL-2, IL-2R, and Ig sequence elements with different affinities, thereby affecting the magnitude of gene expression. Interestingly, this factor also binds to other cytokine genes, such as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and HIV-1 and HTLV-1 LTR sequences.
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PMID:Involvement of a common transcription factor in the regulated expression of IL-2 and IL-2 receptor genes. 251 55

By using target cells that expressed isolated env, gag, p27nef, or p23vif molecules introduced by recombinant vaccinia viruses containing genes encoding these polypeptides, it was possible to identify env, gag, p27nef, and p23vif as cytolytic target antigens for freshly isolated blood cells from human immunodeficiency virus 1 (HIV-1) seropositive patients. Most of the patients tested (95%) manifested a specific cytotoxic activity against vaccinia virus-env-infected target cells. The env-specific cytotoxic activity was not restricted by the major histocompatibility complex and was not mediated by T lymphocytes, as shown by the absence of blocking effect with an anti-CD3 monoclonal antibody and by the inefficiency of CD3+, CD8+, or CD4+ and CD8+ depletion to reduce the cytotoxic activity against the env-expressing target cells. In the same conditions, the cytotoxic activity specific for gag was abrogated and gag major histocompatibility complex-restricted cytotoxic T lymphocytes were detected in 85% of the subjects tested. Therefore, in a HIV-1 seropositive subject, distinct types of effector cells mediate the lysis of target cells expressing gag and env proteins.
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PMID:Human immunodeficiency virus-specific cytotoxic responses of seropositive individuals: distinct types of effector cells mediate killing of targets expressing gag and env proteins. 252 99

The pathogenesis of cellular immune deficiency following human immunodeficiency virus (HIV) infection could result from quantitative and/or qualitative dysfunction of the CD4+ lymphocyte population. To better characterize the T-cell response to soluble antigen with HIV infection, we have isolated peripheral blood lymphocytes and purified populations of CD4+ lymphocytes from healthy HIV antibody-positive subjects, patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and healthy HIV antibody-negative controls. T-lymphocyte function was determined by proliferative response to lectin (phytohemagglutinin), phorbol 12-myristate 13-acetate (PMA), calcium ionophore, purified recombinant HIV envelope gp120, tetanus toxoid antigen, and tetanus toxoid antigen in the presence of recombinant gp120 or purified recombinant soluble CD4. PBLs and CD4+ lymphocytes from asymptomatic HIV-infected subjects responded equally well to lectin, PMA, and/or calcium ionophore and to tetanus toxoid as cells from uninfected control subjects. The cells that proliferated in response to a soluble antigenic stimulus did not respond to gp120. Cells from subjects with ARC had a selective antigen recognition defect independent of the number of CD4+ lymphocytes. Recombinant gp120 inhibited CD4+ lymphocyte proliferation to antigenic stimulus by 30-40%. Recombinant soluble CD4, a proposed therapeutic for HIV, had no effect on T-cell response to antigen. A selective antigen recognition response was not compromised early in HIV infection but was compromised in subjects with ARC. Inhibition of proliferation to tetanus toxoid by gp120 suggests that HIV may affect major histocompatibility complex II restricted antigen recognition independent of CD4+ cell loss.
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PMID:CD4+ lymphocyte function with early human immunodeficiency virus infection. 256 77

The complex biological processes responsible for regulating the immune system are presently the subject of considerable interest and study. New insight into this process comes from a variety of observations and it is the purpose of this communication to develop the hypothesis that two seemingly quite disparate observations point to a common biological mechanism bearing on immunoregulation. The observations concern the unique immunologic relationship between mother and fetus and the immunoregulatory abnormalities encountered in HIV-induced acquired immunodeficiency syndrome (AIDS). Exposure to foreign (allo) major histocompatibility complex (MHC) antigens can potentially occur during pregnancy, the transfusion of blood or blood products, or anal insemination. The hypothesis, in its simplest form, states that such MHC alloantigenic exposure triggers a sequence of immunoregulatory mechanisms resulting in immunosuppression and that this response has evolved in placental mammals as a means of protecting the fetus from maternal immune rejection and promoting optimal fetal development.
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PMID:Does exposure to HLA alloantigens trigger immunoregulatory mechanisms operative in both pregnancy and AIDS? 268 27

Friend murine leukaemia virus complex (FV) causes an immunosuppressive retrovirus-induced disease. In certain mouse strains, FV shows striking similarities to human immunodeficiency virus (HIV) infection in man in that infected mice have severe T-cell immunosuppression but also develop virus-neutralizing antibodies incapable of eliminating infected cells. Previously we noted the influence of mouse major histocompatibility complex (H-2) genes on both FV-induced immunosuppression and on ability to protect mice against FV by immunizing with a vaccinia-Friend murine leukaemia helper virus (F-MuLV) envelope (env) recombinant virus. Here we show that different subregions of H-2 are involved in susceptibility to virus-induced immunosuppression (H-2D subregion) and protective immunization with a recombinant vaccinia virus (H-2K or I-A subregions). Thus, susceptibility to virus-induced immunosuppression does not preclude protection by vaccinia-Friend immunization. The mechanism of protection seems to involve priming of immune T cells, and not initial induction of neutralizing antibodies or cytotoxic T lymphocytes (CTL) (ref.2). Subsequent virus challenge generates a secondary response, resulting in appearance of IgG antibodies and CTL. In human HIV infection there could also be host genetic influences on elements of disease pathogenesis, such as immunosuppression, and on the success of T-cell priming by potential protective vaccines.
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PMID:Different H-2 subregions influence immunization against retrovirus and immunosuppression. 282 42

Forty-one patients seropositive for human immunodeficiency virus type 1 (HIV-1) were assessed for cell-mediated cytotoxicity (CMC) against autologous target cells bearing the major envelope glycoprotein of HIV-1, gp120. Effector lymphocytes from over 85% of seropositive patients showed CMC specific for gp120-coated targets, whereas seronegative individuals had no detectable CMC. As a group, symptomless individuals had the highest levels of CMC; patients with AIDS-related complex and AIDS showed progressively diminished reactivity. The gp120-specific CMC was mediated by a population of non-T-cell effectors phenotypically resembling NK/K cells. Cytolysis was not restricted by major histocompatibility complex determinants, as shown by killing of heterologous gp120-adsorbed targets and of HIV-1-infected cell-lines. Gp120-specific CMC was highly augmented in the presence of interleukin 2, so it may be possible to develop therapeutic strategies aimed at destruction of virus-producing cell reservoirs in infected individuals through stimulation of HIV-specific host CMC.
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PMID:Cellular anti-GP120 cytolytic reactivities in HIV-1 seropositive individuals. 289 30

CD4 (T4) is a glycoprotein of relative molecular mass 55,000 (Mr 55K) on the surface of T lymphocytes which is thought to interact with class II MHC (major histocompatibility complex) molecules, mediating efficient association of helper T cells with antigen-bearing targets. The CD4 protein is also the receptor for HIV, a T-lymphotropic RNA virus responsible for the human acquired immune deficiency syndrome (AIDS) (refs 4-7). To define the mechanisms of interaction of CD4 with the surface of antigen-presenting cells and with HIV, we have isolated the CD4 gene and expressed this gene in several different cellular environments. Here we describe an efficient expression system in which a recombinant, soluble form of CD4 (sCD4) is secreted into tissue culture supernatants. This sCD4 retains the structural and biological properties of CD4 on the cell surface, binds to the envelope glycoprotein (gp110) of HIV and inhibits the binding of virus to CD4+ lymphocytes, resulting in a striking inhibition of virus infectivity.
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PMID:A soluble form of CD4 (T4) protein inhibits AIDS virus infection. 325 44

Priming of CD8+ cytotoxic T lymphocyte (CTL) responses with recombinant proteins has been facilitated by the development of novel adjuvants that deliver antigens into the class I major histocompatibility complex (MHC) pathway. However, the extent to which secondary structure or glycosylation of these proteins prevents priming of class I MHC-restricted CTL responses is not clear. To address this issue, recombinant HIV-1 gp120 envelope proteins produced in yeast insect, or mammalian cells were compared for the ability to elicit CD8+ CTL activity in mice. Envelope-specific CD8+ T lymphocytes were detected in BALB/c mice immunized with env 2-3, a 55-kDa yeast-derived envelope protein that is not glycosylated and lacks a native conformation. This response was directed against a previously described epitope in the V3 region of gp120, as well as a newly identified epitope located near the carboxy-terminus of the molecule. Similar levels of V3-directed CTL activity were observed in mice immunized with recombinant gp120 produced in insect (Spodoptera fugiperda) cells using a baculovirus expression system (gp120BAC). In contrast, induction of CTL responses was considerably less efficient when mice were immunized with gp120CHO, a native, fully glycosylated envelope protein produced in mammalian CHO cells. Denaturation of gp120CHO prior to immunization was not sufficient to prime CTL responses. However, envelope-specific CD8+ CTL activity was elicited when N-linked glycans were removed by treatment with an endoglycosidase. Possible mechanisms by which N-linked glycans influence delivery or processing of recombinant proteins for class I MHC presentation, and the implications of these findings for the design of subunit vaccines, are discussed.
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PMID:Induction of HIV-1 envelope (gp120)-specific cytotoxic T lymphocyte responses in mice by recombinant CHO cell-derived gp120 is enhanced by enzymatic removal of N-linked glycans. 752 39

To increase the inherently weak immunogenicity of synthetic peptide vaccines, we used recombinant DNA techniques to generate chimeras between immunogenic determinants of human immunodeficiency virus type 1 (HIV-1) gp120 and antibody Fab fragments reactive with surface structures displayed specifically on human antigen-presenting cells (APCs), including surface immunoglobulin D (sIgD) and class II major histocompatibility complex (MHC) molecules. Hybridomas producing anti-human MHC class II (HLA-DR) or surface immunoglobulin D monoclonal antibodies (MAbs) that recognize nonpolymorphic determinants were used to clone chimeric Fab gene fragments by employing an established procedure to generate antigen-binding Fab libraries in phagemid vector pComb3. Molecular and immunochemical analysis indicated that the expected chimeric Fab fragments expressing the HIV-1 epitopes were correctly cloned and expressed in Escherichia coli and retained the binding specificity of the native (hybridoma-derived) MAb. The chimeric Fab fragments targeted the linked HIV-1-derived antigenic determinants to the surface of human APCs in vitro, as evidenced by fluorescence-activated cell sorter analysis. Furthermore, such recombinant immunotargeted HIV-1 peptide antigens demonstrated improved immunogenicity over equivalent nonimmunotargeted control antigens, as shown by their ability to stimulate interleukin-2 production by CD4+ T-helper cells from human donors exposed to HIV-1 antigens. These data suggest that immunotargeting of recombinant peptide antigens via the attached Fab fragments facilitates uptake by human APCs with subsequent access to the MHC class II processing pathway, thereby validating the immunotargeting concept for such recombinant subunit vaccines in an in vitro human system.
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PMID:Immunogenic targeting of recombinant peptide vaccines to human antigen-presenting cells by chimeric anti-HLA-DR and anti-surface immunoglobulin D antibody Fab fragments in vitro. 753 57

CD4 is the predominant cell membrane protein that binds human immunodeficiency virus type 1 (HIV-1) gp120 and facilitates HIV-1 infection, but other membrane-associated molecules may be involved in determining HIV-1 cellular infection. Our prior work had suggested that CD44, the transmembrane receptor for hyaluronan, might play a role in the infection of mononuclear phagocytes with HIV-1. In the present work, we have used cells of the CD4-positive, CD44-negative human T-lymphoblast cell line Jurkat to study the role of CD44 in HIV-1 infection and tropism. Cells were transfected with cDNA for the standard (S, or hematopoietic) CD44 isoform CD44S or the epithelial isoform CD44E. The resultant lines expressed appropriate CD44S or CD44E mRNA and protein. While the parent Jurkat cells, those transfected with vector alone, and those transfected with CD44E could be productively infected with only the lymphocytotropic strain HIV-1-LAI, cells transfected with CD44S were rendered susceptible to productive infection with the monocytotropic strains HIV-1-BaL and HIV-1-ADA. Also, CD44S-transfected cells displayed higher levels of infection with HIV-1-LAI than did the other transfected Jurkat cells. The transfected cell line cells all had comparable growth rates and expressed similar levels of the membrane antigens CD4, CD7, major histocompatibility complex (MHC) class I, MHC class II, and CD11a, while levels of CD3 were slightly higher in cells transfected with vector alone and in one of the clones transfected with CD44S. Hyaluronan binding was increased in cells transfected with either CD44S or CD44E. Mouse NIH 3T3 fibroblasts transfected with human CD4, human CD44S, or both human CD4 and CD44S displayed the appropriate antigens, but they could not be productively infected with lymphocytotropic or monocytotropic strains of HIV-1. The results indicate that in human leukocytes, CD44S is an important determinant of HIV-1 productive infection and may be involved in viral cellular tropism.
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PMID:Cellular CD44S as a determinant of human immunodeficiency virus type 1 infection and cellular tropism. 753 3


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