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

Increased levels of serum IgE and eosinophilia have been described in human immunodeficiency virus (HIV) infection, almost exclusively in patients with CD4+ cell count < 200 cells/microliters. IgE production is regulated by CD4+ T helper type 2 (Th-2) lymphocytes, producing interleukin 4 (IL-4) and expressing a ligand for the B cell-specific CD40 molecule (CD40 ligand [L]). A shift to a Th-2-like pattern of cytokine secretion has been postulated to be associated with progression toward acquired immunodeficiency syndrome (AIDS). We studied three AIDS patients with very high levels of IgE and almost complete depletion of CD4+ lymphocytes, suggesting that IgE synthesis could not be driven by CD4+ cells. IgE in vitro synthesis by cells from such patients was, however, inhibited by anti-IL-4. We show that both CD8+ T cell lines and the majority of CD8+ T cells clones derived from these patients produce IL-4, IL-5, and IL-6 in half of the cases together with interferon gamma (IFN-gamma). 44% of CD8+ T cell clones expressed a CD40L, and the supernatants of the clones were capable of inducing IgE synthesis by normal B cells costimulated with anti-CD40. CD8+ T cells in these patients therefore functionally mimic Th-2 type cells and may account for hyper-IgE and eosinophilia in the absence of CD4+ cells. The presence of such CD8+ cells may also provide a source of IL-4 directing the development of predominant Th-2 responses in HIV infection.
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PMID:CD8+ T lymphocytes provide helper activity for IgE synthesis in human immunodeficiency virus-infected patients with hyper-IgE. 780 25

Different experimental approaches were used to prove or disprove the "TH1/TH2 switch theory" of HIV-infection. No increase, or even a decrease, in the production of TH2-type cytokines (IL-4, IL-5, and IL-10) by either bulk circulating mononuclear cells or CD4+ T-cell clones generated by PHA stimulation of single T cells from HIV-infected individuals in all stages of disease compared to HIV-negative donors was observed. However, enhanced proportions of CD4+ T-cell clones able to produce both TH1-type and TH2-type cytokines (TH0 clones) were derived from either skin-infiltrating, in vivo-activated, T cells or in vitro antigen-stimulated peripheral blood T cells of HIV-infected individuals. Of note, TH1, TH2 and TH0 clones obtained from HIV-seronegative healthy donors showed different ability to support viral replication after infection with HIV in vitro. All TH2 and most TH0 clones supported HIV replication efficiently, whereas TH1 clones did not. These results suggest preferential HIV replication in T cells producing TH2-type cytokines rather than TH1/TH2 switch in HIV infection.
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PMID:Role of TH1/TH2 cytokines in HIV infection. 782 29

The potential for eliciting humoral and cytotoxic T lymphocyte (CTL) responses to HIV-1 gp120 by gene gun-based DNA immunization in mice was examined. We speculated that the induction of de novo antigen production in the epidermis of BALB/c mice following particle bombardment-based gene delivery would result in both MHC class I- and class II-mediated antigen presentation for the elicitation of CTL and antibody responses, respectively. Following epidermal delivery of microgram quantities of an expression plasmid, gp120 production resulted in the appearance of MHC class I-restricted, CD8+ CTL responses. gp120-specific CTL responses peaked following a booster immunization, then declined with the appearance of gp120-specific IgG responses when additional booster immunizations were administered. This qualitative progression in the nature of gp120-specific immune responses with subsequent immunizations was paralleled by a simultaneous shift in the interferon-gamma and interleukin 4 release profiles following antigen stimulation of splenocytes in vitro. The simultaneous shifts in immune responses and cytokine release profiles indicate that the progression of antigen-specific CTL and IgG responses in gp120 DNA-immunized mice may be mediated through changes in the in vivo production of cytokines, such as those associated with the Th1 and Th2 subsets of CD4+ cells.
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PMID:A qualitative progression in HIV type 1 glycoprotein 120-specific cytotoxic cellular and humoral immune responses in mice receiving a DNA-based glycoprotein 120 vaccine. 788 98

Defining the factors and/or mechanisms that lead to the predominance of a particular CD4+ T-cell subset (Th-1 vs. Th-2) is an area of intense investigation. In murine schistosomiasis, Th-2-type T cells become predominant after deposition of eggs. The most immunoreactive egg components are glycoproteins. Previously we identified two interesting oligosaccharides found on schistosome eggs and schistosomula. One, lacto-N-fucopentaose III (LNFP-III) contains the interesting trisaccharide Lewisx, which is a weak ligand for P-selectin and is a sugar also found on the alpha and beta chains of the integrin lymphocyte function-associated molecule 1, a ligand for intercellular adhesion molecule 1. Because of the correlation between schistosome egg glycoproteins and Th-2 dominance, the present study examined whether LNFP-III and structurally related oligosaccharides were lymphostimulatory and/or able to induce factors known to down-regulate Th-1 cells. We found that LNFP-III and related sugars did induce proliferation of splenic non-T cells, B220+,CD4-,CD8- cells (B cells) of schistosome-infected and naive mice. In contrast to proliferation, LNFP-III was the only oligosaccharide that induced spleen cells to produce large amounts of interleukin 10 and prostaglandin E2, two molecules known to down-regulate Th-1 cells. Further, only spleen cells from infected mice produced cytokines after oligosaccharide stimulation. Interestingly, LNFP-III stimulation did not induce production of interleukin 4. Thus, a specific carbohydrate ligand has been identified that stimulates B cells to proliferate and produce factors that down-regulate Th-1 T cells. Further, we suggest that identical or structurally related ligands may contribute to the known Th-1 down-regulation in other parasitic diseases and in chronic blood-vascular diseases such as human immunodeficiency virus infection and a number of metastatic carcinomas and that this effect may, therefore, be a general phenomenon.
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PMID:Oligosaccharide-specific induction of interleukin 10 production by B220+ cells from schistosome-infected mice: a mechanism for regulation of CD4+ T-cell subsets. 827 49

We have analyzed the V beta usage by CD4+ and CD8+ T cells from human immunodeficiency virus (HIV)-infected individuals in response to an in vitro stimulation with the superantigenic erythrogenic toxin A (ETA) of Streptococcus pyogenes. ETA amplifies specifically CD4+ and CD8+ T cells from control donors expressing the V beta 8 and the V beta 12 elements. When peripheral T cells from asymptomatic HIV-infected individuals were stimulated with ETA, there was a complete lack of activation of the V beta 8+ T cell subset, whereas the V beta 12+ T cell subset responded normally to the superantigen. This V beta-specific anergy, which was also observed in response to staphylococcal enterotoxin E (SEE), affected both CD4+ and CD8+ T cells and represented an intrinsic functional defect rather than a specific lack of response to bacterial superantigens since it was also observed after a stimulation with V beta 8 monoclonal antibodies. The V beta 8 anergic T cells did not express interleukin 2 receptors (IL-2Rs) and failed to proliferate in response to exogenous IL-2 or IL-4, suggesting that this anergy was not a reversible process, at least by the use of these cytokines. The unresponsiveness of the V beta 8 T cell subset is frequent since it was found in 56% of the patients studied, and comparison of the clinical status of responder vs. anergic patients indicated that the only known common factor between them was HIV infection. In addition, it is noteworthy that the anergy of the V beta 8 subset may be a very early phenomenon since it was found in a patient at Centers for Disease Control stage I of the disease. These data provide evidence that a dominant superantigen may be involved in the course of HIV infection and that the contribution of HIV has to be considered.
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PMID:Selective anergy of V beta 8+ T cells in human immunodeficiency virus-infected individuals. 790 16

CD8+ cells from HIV-infected individuals inhibit HIV replication in cultured CD4+ cells by a nonlytic, non-MHC-restricted mechanism. The activity appears to be mediated in part by a soluble antiviral factor (CAF) secreted by the CD8+ cells. In an attempt to identify this factor a large panel of recombinant cytokines was examined for their effect on HIV replication in CD4+ cells. In addition to interferon-alpha and -beta, TNF alpha, TGF beta, and IL-8 reduced virus replication in a dose-dependent fashion. In some cases, the effect of the cytokine was also dependent on the HIV infection assay used to measure it. Antibodies against the inhibitory cytokines, as well as antibodies against TNF beta, IFN-alpha, IFN-beta, IL-4, and IL-6 did not inactivate the antiviral effect of CAF. The data suggest that CAF does not have identity with known antiviral cytokines and therefore CAF may be a novel antiviral factor.
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PMID:Effect of cytokines on HIV replication in CD4+ lymphocytes: lack of identity with the CD8+ cell antiviral factor. 790 3

The T cell repertoire to human immunodeficiency virus (HIV) was studied in HIV-infected patients of different clinical stages by the detection and enumeration of cells that secreted interferon gamma (IFN-gamma) in short-term cultures of blood mononuclear cells after stimulation in vitro with the HIV recombinant antigens pB1, p121, p24-15, gp160bac, and the HIV V3 loop peptide. T cell reactivities to cytomegalovirus (CMV) and Mycobacterium tuberculosis-purified protein derivative (PPD) were examined in parallel. Among 29 patients with HIV infection, 48% had blood cells recognizing one or more of the five HIV antigens. The mean numbers of HIV antigen-reactive T cells varied between 1/approximately 6000 blood cells for pB1 and 1/approximately 20,000 cells for p24-15. None of the five HIV antigens studied was identified as an immunodominant T cell epitope in HIV infection. T cells from 20% of the patients responded to all five HIV antigens in parallel, but the antigen preferentially recognized varied from patient to patient. Those with more advanced disease had a tendency to lower numbers of HIV antigen-reactive T cells. Most HIV-infected patients had both CMV- and PPD-reactive T cells, but numbers were significantly lower in more advanced disease. It should be possible to adopt the present method to evaluate fine specificities of the T cell repertoire to other antigens and to study the involvement of other cytokines besides IFN-gamma, for example, the Th2 cell-related cytokine interleukin 4.
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PMID:HIV antigen-reactive T cells detected by antigen-induced interferon gamma secretion. 791 Oct 28

In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were studied for their regulation of HIV expression in monocytes. Pretreatment of peripheral monocytes for 48-72 h with IL-13 markedly decreased acute HIV infection, whereas IL-4 increased it. Similar effects were seen when the U1 and R-THP-1 monocytoid cell lines with restricted HIV expression were treated with these cytokines. However, when these continuously producing cell lines were chronically treated with cytokines, IL-13 increased HIV production. Neither IL-4 nor IL-13 stimulated HIV expression in latently infected cells. In chronically infected cells, several cytokines reduced viral mRNA. Both IL-4 and IL-13 increased monocyte aggregate formation, but only IL-4 ultimately stimulated cytolysis of HIV-infected monocytes as well as increased apoptosis of U1. In the presence of tumor necrosis factor alpha or IL-6, which upregulate HIV expression, IL-13 could no longer suppress HIV expression. These results indicate that IL-4 and IL-13, although closely related in modulating monocyte function, can have divergent effects on HIV expression in monocytes. Collectively, these data suggest that there exists a complex cytokine tissue environment with positive regulators of HIV expression able to override negative regulators.
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PMID:IL-4 and IL-13 have overlapping but distinct effects on HIV production in monocytes. 791 30

CD8+ T cells activated in the presence of IL-4 can develop into distinct, non-cytotoxic CD8- and cytotoxic CD8+ subsets that produce IL-4, IL-5, IL-10 but do not produce IFN-gamma. These 'Th2 like' CD8+ cells may enhance Th2 responses, help B cells or suppress Th1 immune responses. Importantly, the switch from the cytotoxic, IFN-gamma producing CD8+ T-cell phenotype could compromise the host response to infectious agents such as HIV.
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PMID:Non-cytotoxic, IL-4, IL-5, IL-10 producing CD8+ T cells: their activation and effector functions. 791 14

Interleukin-12 (IL-12) is a disulfide-linked heterodimeric cytokine originally identified as a product of EBV-transformed B cell lines. Monocyte/macrophages are the physiologically most relevant producers of IL-12, in response to both Gram-positive and -negative bacteria, bacterial products, and intracellular parasites. Although IL-12 has an enhancing effect on the survival and growth of early hematopoietic progenitor cells, most of the IL-12 biological activity has been described on T and NK cells, on which it induces production of lymphokines, primarily IFN-gamma, enhances cytotoxic activity, and, in cooperation with other stimuli, increases proliferation. IL-12 is an inducer of development of T helper type 1 (Th-1) cells and the equilibrium between IL-12 and IL-4 is probably important for the balance in vivo between Th-1 and Th-2 responses. IL-12 has an important role in the host resistance to infection, in particular to intracellular pathogens, by activating macrophages through induction of IFN-gamma from NK and T cells and by enhancing cell-mediated immune responses, dependent on Th-1 cell development. Peripheral blood mononuclear cells from HIV-seropositive individuals are impaired in their ability to produce IL-12 in response to bacterial stimulation, and IL-12 restores in vitro some of the depressed immunological functions, suggesting that a defect in IL-12 production may have a pathogenic role in the immunodeficiency of HIV-infected individuals. Natural IL-12 appears to provide a regulatory link between innate resistance and the development of the antigen-specific adaptive immune response and the recombinant protein has therapeutic potential because of its activity against tumors and infections and its effectiveness as an adjuvant enhancing cell-mediated immunity in vaccination.
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PMID:Interleukin-12: a bridge between innate resistance and adaptive immunity with a role in infection and acquired immunodeficiency. 792 92


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