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

Certain maternal/infant pairs, as well as other high-risk adults, develop a host-response HIV-1 infection characterized by circulating and tissue infiltrative CD8 T-cell lymphocytosis, termed Diffuse Infiltrative Lymphocytosis Syndrome (DILS). DILS primarily occurs in the salivary glands, lungs, renal interstitium, and gastrointestinal tract. DILS differs from Sjogren's syndrome in the degree of salivary gland enlargement, high frequency of extraglandular manifestations, paucity of autoantibodies, and distinct immunogenetic associations. Salivary gland B-cell lymphoma is a complication common to both conditions. The circulating CD8 T cells in DILS have a memory phenotype. Egress into target tissues involves adhesion molecule receptor-ligand interactions, apparently in response to the local presence of HIV-1. Immunogenetic predisposition involves interaction between both MHC classes I and II loci. This disease appears to reflect a specific host response that leads to persistence of monocyte-tropic, rather than T-cell-tropic, HIV-1 strains, in an analogous fashion to Visna Maedi virus disease in sheep. The development of DILS in children appears to be regulated in a dominant fashion by maternally or paternally inherited MHC class II alleles in response to transplacentally or perinatally acquired maternal HIV-1 strains.
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PMID:Diffuse infiltrative lymphocytosis syndrome in children and adults infected with HIV-1: a model of rheumatic illness caused by acquired viral infection. 128 93

Since alterations of epidermal Langerhans cells (LC) have been observed in humans infected with HIV, we investigated the morphology and function of these cells in murine acquired immunodeficiency syndrome (MAIDS), a murine model closely resembling human AIDS. The number as well as the shape of dendritic MHC class II+ cells from ear skin of C57BL/6 mice were similar in normal and infected animals. In mixed epidermal cell (EC) lymphocyte cultures, EC from infected mice and from normal mice stimulated allogeneic T cell proliferation to the same extent. In contrast to T cells from normal mice, however, T cells from infected mice did not respond to allogeneic spleen cells, confirming the presence of a T-cell defect in MAIDS. Subcutaneous injection of syngeneic mice with trinitrophenyl-modified MAIDS EC resulted in delayed ear swelling responses after challenge that were equivalent to those induced by hapten-modified EC from normal mice, suggesting that the contact sensitivity inducing potential of MAIDS LC was preserved. To investigate antigen presenting and processing function, EC and spleen cells were tested with the ovalbumin-specific IAb-restricted T cell hybridoma BO.17.10 and either ovalbumin 323-339 peptide or intact ovalbumin protein. MAIDS spleen cells had a reduced antigen presenting capacity compared with normal spleen cells, whereas EC from these mice showed the same processing and presenting capacity as normal controls. In summary, our results demonstrate that the frequency, morphology, level of MHC class II antigen expression and ability to process and present antigen is normal for LC from mice with MAIDS whereas the function of splenic T cells and APC from infected mice is significantly impaired.
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PMID:Epidermal and splenic antigen-presenting cell function in a retrovirally induced murine immunodeficiency syndrome (MAIDS). 132 74

A few cases have been described of antigenic determinants that are broadly presented by multiple class II MHC molecules, especially murine I-E or human DR, in which polymorphism is limited to the beta chain, and the alpha chain is conserved. However, no similar cases have been studied for presentation by class I MHC molecules. Because both domains of the MHC peptide binding site are polymorphic in class I molecules, exploring permissiveness in class I presentation would be of interest, and also such broadly presented antigenic determinants would clearly be useful for vaccine development. We had defined an immunodominant determinant, P18, of the HIV-1 gp160 envelope protein recognized by human and murine CTL. To determine the range of class I MHC molecules that could present this peptide and to determine whether two HIV-1 gp160 Th cell determinants, T1 and HP53, could also be presented by class I MHC molecules, we attempted to generate CTL specific for these three peptides in 10 strains of B10 congenic mice, representing 10 MHC types, and BALB/c mice. P18 was presented by at least four different class I MHC molecules from independent haplotypes (H-2d, p, u, and q to CD8+ CTL. In H-2d and H-2q the presentation was mapped to the D-end class I molecule, and for Dd, a requirement for both the alpha 1 and alpha 2 domains of Dd, not Ld, was found. HP53 was also presented by the same four different class I MHC molecules to CD8+ CTL although at higher concentrations. T1 was presented by class I molecules in three different strains of distinct MHC types (B10.M, H-2f; B10.A, H-2a; and B10, H-2b) to CTL. The CTL specific for P18 and HP53 were shown to be CD8+ and CD4- and to kill targets expressing endogenously synthesized whole gp160 as well as targets pulsed with the corresponding peptide. To compare the site within each peptide presented by the different class I molecules, we used overlapping and substituted peptides and found that the critical regions of each peptide are the similar for all four MHC molecules. Thus, antigenic sites are broadly or permissively presented by class I MHC molecules even without a nonpolymorphic domain as found in DR and I-E, and these sequences may be of broad usefulness in a synthetic vaccine.
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PMID:Broad recognition of cytotoxic T cell epitopes from the HIV-1 envelope protein with multiple class I histocompatibility molecules. 137 84

Pneumocystis carinii pneumonia (PCP) is a well-recognized cause of morbidity in patients with impaired T-cell function. In this study of cellular immunity to P. carinii, peripheral blood mononuclear cells from 25 HIV antibody-positive (HIV+) patients and 11 healthy individuals were stimulated in vitro with P. carinii antigen. The responding T-cell blasts were cocultured with autologous P. carinii antigen-pulsed macrophages to measure P. carinii-specific cytolytic T-lymphocyte activity (CTL). T-cell blasts from two healthy donors were used to generate P. carinii-specific clones by limiting dilution. T cells from HIV+ patients proliferated less to P. carinii antigen than T cells from healthy volunteers. In contrast, the level of specific cytotoxicity was identical in all groups when equal numbers of CTLs were used. Within the group of symptomatic patients, CTL activity was higher in those with a history of PCP (p = 0.033). Pneumocystis carinii antigen-specific T-cell clones proved to be CD4+ and MHC class II restricted; six of eight clones tested showed P. carinii-specific cytolytic activity. Cell-mediated immune response to P. carinii in healthy individuals include CD4+, class II MHC-restricted T cells with P. carinii-specific cytotoxicity. There is an increasing loss of P. carinii-specific proliferative responses in HIV+ patients as disease progresses, but a cytotoxic response is still detected in the absence of proliferation.
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PMID:T-lymphocyte responses to Pneumocystis carinii in healthy and HIV-positive individuals. 137 54

The CTL response to HIV-1 is more vigorous than for any known human pathogen and may be a significant factor in preventing the progression to symptomatic disease. T cell lines, generated by non-specific stimulation with PHA and IL-2, may be reproducibly used to identify HIV-1 isolate-invariant epitopes recognized by the CTL of infected individuals. The CTL response in each of 12 infected individuals to envelope and reverse transcriptase (RT) is dominated by the recognition of one or two viral isolate-invariant epitopes. Seven subjects respond to a single gp160 epitope; three subjects recognize 2 gp160 epitopes. There is a significant increase in recognition of epitopes in the C terminal 104 amino acids of gp41 (p less than 0.002); in fact 40% of the subjects that respond to gp160 recognize the C terminal 20-mer. The CTL-mediated lysis of gp160-expressing targets is MHC restricted, but not all individuals that share the same serologically defined class I-restricting element respond to the same epitope. Recognition of the terminal 20mer is restricted by both A30 and B8. The response to RT in six subjects is distributed over the RT protein. The six subjects recognize four separate regions defined by truncated RT-vaccinia recombinants, but none of the subjects' CTL demonstrate significant recognition of the RT epitope identified in H-2k mice and some humans.
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PMID:Cytotoxic T lymphocytes from HIV-1 seropositive individuals recognize immunodominant epitopes in Gp160 and reverse transcriptase. 137 97

To understand better the specificity of peptide binding by MHC class I molecules, we have evaluated the capacity of a panel of unrelated peptides to compete for the presentation of viral peptides presented by HLA-A3 and HLA-B27. The HIV-Nef7F peptide (74-82) was presented by HLA-A3 to Nef-specific HLA-A3-restricted CTL lines, and the influenza nucleoprotein peptide NP(380-393) was presented by HLA-B27 to NP(380-393)-specific HLA-B27-restricted CTL lines. In addition, we have extended studies from our group that have evaluated the capacity of a similar panel of peptides to inhibit presentation of an influenza nucleoprotein peptide NP (335-349) by HLA-B37 and a matrix peptide, M1 (57-68), by HLA-A2 to the appropriate peptide-specific CTL lines. Out of 41 peptides tested, only five bound to more than one of the MHC molecules analyzed. Pairwise comparisons of the peptide binding specificities among these four different class I molecules revealed no common competitor peptides in four of the six possible comparisons. Thus, each class I molecule appears to have a functionally distinct peptide binding site, as reflected by the ability to bind largely non-overlapping sets of peptides.
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PMID:The peptide binding specificity of HLA class I molecules is largely allele-specific and non-overlapping. 137 81

CTL lines specific for two different proteins derived from the human pathogens, Plasmodium falciparum (malaria) circumsporozoite protein and HIV-1 reverse transcriptase, were obtained by immunizing mice with protein-pulsed syngeneic spleen cells. The lysis of the target cells was dependent on a class I MHC molecule and the accessory molecule CD8. Immunodominant epitopic peptides were identified previously in the two proteins using murine CTL derived after immunization with recombinant virus or sporozoites, or using CTL from HIV-1-infected patients. These peptides were also recognized by the CTL lines obtained after protein-pulsed spleen-cell immunization. A new CTL antigenic determinant was localized in HIV-1 reverse transcriptase to residues 514 to 528, a sequence that, if folded as an alpha-helix, would be strongly amphipathic. The determinant was tentatively narrowed, using overlapping peptides, to a core of at least nine residues, 515 to 523. This site was also recognized by CTL obtained by the two different methods of immunization. Therefore, extracellular proteins incubated with spleen cells can be processed and presented in vivo in the same way as intracellular proteins, resulting in recognition of the same epitopes in association with the same class I MHC molecules. The potential implications for vaccine development and for the understanding of class I-restricted Ag presentation are discussed.
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PMID:Immunization with soluble protein-pulsed spleen cells induces class I-restricted cytotoxic T lymphocytes that recognize immunodominant epitopic peptides from Plasmodium falciparum and HIV-1. 138 39

The role of natural killer (NK) cells and their inducible counterparts, lymphokine-activated killer (LAK) cells in AIDS with regard to HIV-1 viral immunosurveillance and the control of secondary opportunistic disease has yet to be established. In this study, we have demonstrated that LAK cells derived from all HIV-1+ groups showed striking increases in their capacity to lyse HIV-1-infected U-937 cells relative to their uninfected U-937 counterparts. Surprisingly, similarly derived LAK cells from healthy seronegative controls showed no differences in their lysis of HIV-1-infected versus uninfected U-937 cells. The differential ability of LAK effectors from seropositive donors to lyse HIV-1-infected targets was demonstrable using a number of U-937 subclones and their HIV-1-infected counterparts. Again, no differences in LAK cell-mediated lysis of HIV-1-infected and uninfected U-937 subclones were observed in seronegative individuals. Our findings that HIV-1+ individuals show selective expansion of non-MHC restricted, HIV-1-directed cytotoxic LAK cells indicate that natural immunity may indeed play a role in HIV-1 viral immunosurveillance.
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PMID:Increased LAK activity against HIV-infected cell lines in HIV-1+ individuals. 138 Dec 98

The inflammatory myopathies encompass a group of heterogenous muscle diseases which have in common an acquired myopathy with histological signs of endomysial inflammation. We present evidence based on recently emerged clinical, histologic, immunopathologic, demographic and therapeutic observations that these myopathies comprise three major and distinct groups: polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis (IBM). Immune-mediated mechanisms characteristic for each group appear to play a primary role in the pathogenesis of these diseases. In DM there is an intramuscular microangiopathy mediated by the C5b-9 membranolytic attack complex, leading sequentially to loss of capillaries, muscle ischemia, muscle fiber necrosis and perifascicular atrophy. In contrast, in PM and IBM the muscle fiber injury is initiated by sensitized CD8+ cytotoxic T cells that recognize MHC-I restricted muscle antigens, leading to phagocytosis and fiber necrosis. Among the viruses implicated in the cause of inflammatory myopathies, only the retroviruses, HIV, HTLV-1 and simian retroviruses, have been convincingly associated with PM. Retroviruses, therefore, appear to be the leading group of viruses capable of triggering these diseases. The treatment of inflammatory myopathies has been largely empirical. A detailed therapeutic plan based on our experience with a large number of patients is presented. Patients with bona fide PM or DM respond to steroids to some degree and for some period of time. In contrast, patients with IBM do not respond to any therapy and the disease should be suspected when a patient with presumed PM has failed treatment. Methotrexate and cyclophosphamide are disappointing. Cyclosporine and Azathioprine are commonly used but they are of uncertain benefit. Plasmapheresis is ineffective. High-dose intravenous immunoglobulin is a promising new therapeutic modality.
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PMID:Clinical, immunopathologic, and therapeutic considerations of inflammatory myopathies. 142 35

The recent report that anti-gp120 antibodies can be induced by allogeneic stimuli in experimental animals in the absence of HIV, has focused attention on the structural similarities between gp120 and MHC. Here we report that some HIV+ individuals develop antibodies which similarly react with the gp120 HIV sequence (aa 254-263) and with the HLA-DR beta chains (aa 142-151). As these two peptides share a high level of similarity, we have investigated the role of this gp120 region on HLA class II mediated T cell recognition. The synthetic peptide corresponding to the gp120 HIV sequence aa 254-263 has been tested on T cell line (TCL) activation. Both the PPD-specific and the self-HLA reactive TCL proliferation increased in the presence of this peptide. Prepulsing experiments indicate that this enhancing effect carried out by HIV peptide is exerted at the level of antigen presentation. Moreover, the specificity of this interaction is supported by the fact that a MoAb specific for this HIV peptide blocked the autoreactive TCL proliferation, similarly to the inhibition carried out by anticlass II antibody. These data support the hypothesis that the functional homology between the HIV peptide and the HLA beta chain described may be involved in the pathogenesis of AIDS.
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PMID:A gp120 HIV peptide with high similarity to HLA class II beta chains enhances PPD-specific and autoreactive T cell activation. 142 70


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