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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

Candidate AIDS vaccines consisting of recombinant forms of the HIV-1 envelope glycoprotein induce, in seronegative human volunteers, an env-specific T cell response that includes CD4+, MHC class II-restricted CTL capable of lysing HIV-1-infected target cells. In this study, we have analyzed the production of the cytokines TNF-alpha and lymphotoxin (LT) by a set of env-specific CD4+ human CTL clones. TNF-alpha and LT are of interest because of their potential role in target cell destruction by CD4+ CTL. Our studies focused on the possibility that a cell surface form of TNF-alpha expressed by CTL after physiologic activation with target APC might participate in the cytolytic reactions mediated by these clones. We found that, upon interaction with target cells expressing env epitopes in the context of the appropriate MHC class II molecules, CD4+ CTL released TNF-alpha with kinetics that were rapid, compared with other cytokines, and that were generally similar to the kinetics of target cell destruction. LT secretion was not detected during the time course of the cytolytic reactions. A novel flow cytometric assay was used to show that physiologic activation of CD4+ CTL with target APC induced expression by the CTL of cell surface forms of TNF-alpha. Immunoprecipitations from activated, surface-iodinated CTL clones revealed two forms of surface TNF-alpha, a 26-kDa form, representing the transmembrane precursor of secreted TNF-alpha, as well as the 17-kDa secreted form bound to the cell surface. For a subset of CD4+ CTL, we found that treatment of CTL with cyclosporin A inhibited Ag-induced production of both transmembrane and secreted forms of TNF-alpha but had no effect on cytolysis. Thus, although transmembrane and secreted TNF-alpha produced by HIV-1-specific CD4+ CTL may have important effects in vivo, the rapid destruction of target APC by the set of CD4+ CTL clones described here occurs through a TNF-alpha-independent mechanism.
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PMID:Production of transmembrane and secreted forms of tumor necrosis factor (TNF)-alpha by HIV-1-specific CD4+ cytolytic T lymphocyte clones. Evidence for a TNF-alpha-independent cytolytic mechanism. 135 Oct 88

We found that naive (CD45RA+) CD4 T cells have a lower capacity of adhesion to Epstein-Barr virus (EBV) immortalized B cells than memory (CD45RO+) CD4 T cells, as judged by conjugate formation. This would appear to be due to differences in the expression of adhesion molecules [lymphocyte function-associated antigen (LFA)-1, CD2]. However, kinetic studies showed that the degree of adhesion of naive T cells to B cells was stable over 60 min while that of memory T cells, like that of unseparated CD4 T cells, was characterized by a rapid formation and rapid dissociation of conjugates. This could be explained by a difference in the sensitivity of naive and memory CD4 T cells to down-regulation of antigen-independent adhesion by CD4-MHC class II interaction. Indeed, memory T cells also adhered stably to MHC class II(-) B cells. The adhesion of memory T cells, but not naive T cells, to MHC class II(+) B cells was sensitive to inhibition by OKT4a an anti-CD4 antibody, human immunodeficiency (HIV) gp160 (env) protein and a 12-mer peptide encompassing the 35-46 sequence of the HLA, DR beta 1 domain and previously shown to inhibit activation of HLA class II-restricted CD4 T cell responses. Since MHC class II expression did not influence the degree of conjugate formation by naive or memory CD4 T cells with B cells, CD4-MHC class II interaction does not appear to be involved in binding itself, but may down-regulate the adhesion of memory but not naive CD4 T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antigen-independent adhesion of CD45RA (naive) and CD45RO (memory) CD4 T cells to B cells. 135 61

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

Cytological smears (CS), taken from the lateral border of the tongue of HIV-seropositive patients (HIV+) (n = 34) and of seronegative controls (HIV-) (n = 16), were examined by means of immunocytochemistry (APAAP) for the distribution patterns of different cytokeratins and MHC class II antigens. Compared with HIV- patients in CS of HIV-infected patients cornification associated cytokeratins 10/11 were increased, while the number of keratinocytes positive for cytokeratins 13/16 was comparable in both groups. Expression of simple epithelial cytokeratins 19, rarely observed in CS of HIV- patients, was a frequent findings in CS of HIV+ patients. Keratinocytes positive for MHC class II antigens were observed in CS of 12/34 HIV+, while all control CS were negative. In the group of HIV+ patients no correlation was found between the clinical presence of HL and the expression of cytokeratins or class II antigens. The altered distribution of cytokeratins may reflect local responses to proliferative stimuli or local inflammation due to the presence of microbial antigens or may occur as a general unspecific reaction in the setting of systemic viral infection. This non-invasive technique seems to be a valuable tool to determine the proliferation rate of oral epithelial cells.
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PMID:Distribution of cytokeratins in oral cytological smears of HIV-infected patients. 137 35

Though antibodies against HIV-1 appearing in the course of infection are successfully used for the diagnostic purposes, their accumulation on the earlier step leads to: firstly, to the rapid generation of the immunodeficiency by different mechanisms and secondly, to inefficiency of immunotherapy. One of the causes for immunodeficiency seems to be antibodies which are induced in the HIV-infected person by the HIV peptides homologous to the MHC class II molecules by their amino acid sequences. 73% of HIV-1 positive sera are shown to react with human B-lymphoma cells expressing surface class II molecule. The binding is caused by the antibodies preventing the murine monoclonal anti-HLA.DR Ab interaction with B-lymphoma. Three amino acid sequences are identified in both alpha- and beta-chain of the HLA.DR antigen, these sequences being homologous to HIV-1 gp120 or gp42 molecules for 50 to 70%. Using synthetic peptides it was shown that HIV-1-infected persons contain antibodies which cross-react to the homologous peptides of the HIV-1 and of the MHC class II. It is supposed that such antibodies shield the class II molecule on the surface of their own antigen-presenting cell which may lead to immunodeficiency caused by the anti-HIV-1 antibody.
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PMID:[Mechanisms of immunodeficiency in HIV infection and ways of overcoming it]. 142 54

Aurintricarboxylic acid (ATA) has been shown to block the binding site for both HIV gp120 and mAb anti-Leu 3a on CD4. We have unexpectedly found that brief treatment with > or = 1 micrograms/ml ATA rapidly disengages another mAb, OKT4E, after it has been bound to CD4 on human PBL. OKT4E is specific for a discontinuous epitope overlapping the MHC class II-binding region in the N-terminal CD4 domain. Interestingly, among 10 other mAb tested, only anti-Leu 8, specific for a leukocyte homing receptor is also quickly released from the cells by ATA treatment. Disengagement of the OKT4E mAb is also seen on a CD4-positive cell line (HPB-ALL) and with recombinant soluble CD4 (sCD4) bound to immobilized OKT4E. In all of these cases, disengagement is prevented if OKT4E is cross-linked, or the Leu 3a site is blocked by the mAb, but not by gp120. Photobleaching fluorescence resonance energy transfer (pFRET) measurements suggest that OKT4E is released as an indirect consequence of ATA-evoked conformational changes of CD4. Similar changes were detected as a result of gp120 binding to PBL. These data raise the possibility of a novel type of immunomodulation: induced disengagement of a bound ligand from its Ag.
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PMID:CD4 changes conformation upon ligand binding. 143 Nov 29

We have cloned and sequenced the cDNA for cat CD4. The overall amino-acid sequence of cat CD4 is similar to that from the primate and rodent CD4 molecules, with a 58% identity between the cat and human sequences. Comparison to the crystal structure of human CD4 does, however, reveal unusual features in the second Ig-like domain, D2, of cat CD4. First, a reciprocal substitution between a tryptophan and a cysteine, this latter involved in an intrasheet disulfide bond of human D2, is predicted to generate an intrastrand disulfide bond, a feature rarely observed in an Ig-fold. Second, a large serine-threonine-rich insertion is found between the A and B beta strands of D2. This sequence is a potential O-linked glycosylation site, and should protrude in a region that appears flexible in human CD4. This unusual insertion could affect the interaction of cat CD4 with class II molecules, or with FIV, a feline homolog of HIV. The expression of cat CD4 in different environment, or of a mutated human CD4 carrying the cat insertion, should help in understanding the role of cat CD4 as a putative receptor for FIV, and the CD4/MHC class II interaction.
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PMID:Unusual amino acid sequence of the second Ig-like domain of the feline CD4 protein. 145 4

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

We have investigated Th cell recognition of the HIV core protein p24 by using CD4+ T cell clones derived from cynomolgus macaques immunized with hybrid HIV p24: Ty virus-like particles (VLP). T cell lines from two immunized animals responded to p24: Ty-VLP, control Ty-VLP, purified p24, and whole inactivated HIV, indicating the presence of T cells specific for p24 as well as the Ty carrier protein. The HIV determinants recognized by the T cell lines were identified by using a series of overlapping peptides synthesized according to the sequence of p24. Both T cell lines recognized peptide 11 (amino acids 235-249) and peptide 14 (amino acids 265-279). In addition, one T cell line also responded to peptide 9 (amino acids 215-229). Definitive identification of two T cell epitopes on p24 was confirmed at the clonal level: from a total of four T cell clones generated from one of the T cell lines, two respond specifically to peptide 11 and two to peptide 14. The T cell clones were CD4+ and MHC class II-restricted and secreted IL-2 in response to stimulation with purified p24, inactivated HIV or a single synthetic peptide. The specificity of the Th clones for variant peptides demonstrated cross-reactivity with two simian immunodeficiency virus isolates, but only limited responses to HIV-2 sequences. However, the Th cell epitopes identified on p24 are highly conserved between 12 HIV-1 isolates and were recognized by both of the immunized primates. These sequences may therefore be useful for priming a broadly reactive immune response to HIV-1.
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PMID:HIV p24-specific helper T cell clones from immunized primates recognize highly conserved regions of HIV-1. 168 53


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