PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Antigenic Modulation”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed1998

Modulation of HLA class I antigen and ICAM-2 on endothelial cells after in vitro infection with human cytomegalovirus.

The aim of the present work is to investigate the expression of HLA class I antigen and intercellular adhesion molecule-2 (ICAM-2) on the surface of human umbilical cord endothelial cells (HUVEC) after infection with human cytomegalovirus (HCMV). The expression of HLA class I antigen and ICAM-2 were determined (using antibodies against HLA class I antigen and ICAM-2) by attachment inhibition assay and flow cytometric analysis. Attachment inhibition assay demonstrated that HCMV increased the expression of HLA class I antigen. This was confirmed by flow cytometric analysis, which showed an increase in HLA class I antigen expression on HCMV-infected HUVEC. The results of the expression of ICAM-2 using attachment inhibition assay revealed that ICAM-2 is involved significantly in the increased adhesion of T lymphocytes to HCMV-infected HUVEC. However, flow cytometric analysis revealed that there were no changes in the expression of ICAM-2 on HCMV-infected HUVEC. One possible explanation for this is that HCMV induces the activation of ICAM-2 on the surface of HCMV-infected endothelial cells without affecting its expression.

Antibodies, Monoclonal↗
PubMed2000

HIV-1 and its causal relationship to immunosuppression and nervous system disease in AIDS: a review.

Acquired immune deficiency syndrome (AIDS), caused by human immunodeficiency virus type 1 (HIV-1), has claimed more than 10 million lives over the past 15 years. There are approximately 30 million HIV-positive people worldwide, 89% of whom reside in sub-Saharan Africa and Asia. The intricate relationship between the virus and HIV-related human multisystem pathology prompted scientists to modify many previously established concepts about infectious diseases and immunology, and to test new ones. The results of this work helped resolve many, albeit not all, long-standing problems concerning HIV-1 immune escape, its cellular tropism, and pathogenesis of HIV-related immunosuppression and nervous system disease. The most impressive advances have been made in antiretroviral drug treatment of HIV infection, which has resulted in dramatically reducing AIDS-related mortality, morbidity, and perinatal transmission. However, considering the magnitude of the worldwide HIV-AIDS pandemic, prohibitive cost and unusually exacting nature of combination drug treatment, as well as the emergence of drug-resistant HIV mutants, the disease and virus remain formidable and unpredictable, particularly in the area of prevention and vaccine development. Here, we have reviewed the most pertinent recently published studies of various aspects of HIV/AIDS intended to answer the following questions: what have we learned and what remains to be determined regarding this unorthodox viral disorder?

AIDS Dementia Complex↗
PubMed1974

Modulation of cell-surface antigens of a murine neuroblastoma.

Antisera were produced in rabbits to morphologically differentiated cells from the C1300 murine neuroblastoma (i.e., cells in which process formation was induced by maintenance on serum-free medium for 5 days). These antisera reacted more strongly in the complement fixation reaction with such "differentiated" cells than with "undifferentiated" (nonprocess-bearing) neuroblastoma cells. Adsorption of the antisera with undifferentiated cells removed the reactivity to cells without processes, while the reactivity with serum-free cells which possess processes was retained. Indirect immunofluorescence studies confirmed the results obtained by complement fixation and demonstrated that antibodies to the surface antigens of process-bearing cells could be adsorbed by particulate preparations from brain but not liver, spleen, or kidney. This is the first description of neural-associated cell-surface changes that correlate with the morphological differentiation in culture of neuroblastoma cells.

Adsorption↗
PubMed1976

Vertical displacement of membrane proteins mediated by changes in microviscosity.

Membrane proteins of intact human erythrocytes were labeled with two fluorescent sulfhydryl reagents. The tagged cells were then subjected to simultaneous liposome treatments for either depletion or enrichment of membrane cholesterol content. Cholesterol depletion, which reduces membrane microviscosity, was followed by a series of fluorescence changes all indicating masking of the membrane proteins. Conversely increasing the membrane microviscosity by cholesterol enrichment resulted in an appreciable increase of the protein exposure to the aqueous surrounding. These findings strongly suggest that membrane proteins may be vertically displaced upon changes in lipid fluidity, a mechanism that may play a significant role in modulation of antigens and receptors in vivo.

Cholesterol↗
PubMed1988

neu protooncogene fused to an immunoglobulin heavy chain gene requires immunoglobulin light chain for cell surface expression and oncogenic transformation.

The protein encoded by the neu protooncogene (human gene symbol NGL for neuro/glioblastoma-derived) is a member of the surface receptor/tyrosine kinase family. Though its structure suggests that it can transduce a transmembrane signal, neither its extracellular ligand nor its critical intracellular substrates are known. To explore the functional properties of the protein encoded by neu, we created a fusion gene that joins the cytoplasmic domain of neu to the extracellular portion of an immunoglobulin heavy chain. The localization of the fusion polypeptide can then be controlled by coexpression with immunoglobulin light chain. In the absence of light chain, the heavy chain-neu polypeptide is expressed intracellularly and has no transforming activity. By contrast, in the presence of light chain the fusion polypeptide is expressed at the cell surface and produces tumorigenic foci. Thus, transformation apparently requires expression at the cell surface, where the neu intracellular domain can interact with components that are localized to the plasma membrane. The fusion protein is active in cellular transformation when the transmembrane domain is derived either from neu or from immunoglobulin, indicating that the neu transmembrane domain is not specifically required for transformation, although neu activation in tumors is known to result from a point mutation in this region. The extracellular immunoglobulin heavy and light chain domains of the fusion protein form a functional binding site that allows antigen to modulate its activity, reversing the transforming effect.

Animals↗
PubMed1989

Isolates of human immunodeficiency virus type 1 from the brain may constitute a special group of the AIDS virus.

The biologic, serologic, and molecular properties of isolates of human immunodeficiency virus type 1 (HIV-1) from the central nervous system (CNS) were determined and compared to those of isolates from peripheral blood and lymph nodes. Among these were pairs of CNS and blood isolates obtained from six infected individuals. The data show that HIV-1 isolates from the CNS can be distinguished from peripheral blood isolates by their (i) relative inability to infect established T-cell lines, (ii) reduced cytopathogenicity, (iii) inability to modulate CD4 antigen expression on infected cells, (iv) efficient replication in peripheral blood macrophages, and (v) insensitivity to serum neutralization. Paired CNS and peripheral blood isolates from the same individual also display some differences in cellular tropism. The blood isolates replicate better in T-cell lines and glioma cell lines, whereas the paired CNS isolates replicate more efficiently in primary macrophages. These results suggest that viruses isolated from the CNS of infected individuals may represent a specific HIV-1 subgroup.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Induction of anergy or active suppression following oral tolerance is determined by antigen dosage.

Oral tolerance was generated to hen egg white lysozyme in the mouse or to guinea pig myelin basic protein in the rat by a low-dose (1 mg) or a high-dose (5-20 mg) feeding regimen. High doses of antigen induced tolerance characterized by anergy with little or no active suppression and increased secretion of interleukin 4 (IL-4). Anergy was shown by an increase in frequency of IL-2-secreting cells following culture in recombinant IL-2. Low doses of antigen induced tolerance characterized by antigen-driven active suppression with increased secretion of transforming growth factor beta (TGF-beta) and IL-4 and minimal anergy. Without further immunization, spleen cells from animals orally tolerized by both regimens secreted increased levels of IL-4 and TGF-beta in an antigen-specific manner. Animals fed high doses secreted more IL-4 and less TGF-beta, whereas those fed low doses secreted more TGF-beta and less IL-4. These results demonstrate that the two feeding regimens induced cell populations that differed in their cytokine secretion profile and their capacity to actively suppress in vitro and to induce anergy. Our results provide a basis for distinguishing different forms of antigen-driven peripheral tolerance and have important implications for orally induced antigen-specific modulation of human autoimmune diseases.

Administration, Oral↗
PubMed2001

Oxidative stress induces the expression of the major histocompatibility complex in murine tumor cells.

The effect of t-butyl hydroperoxide (t-BOOH) on the induction of the Major Histocompatibility Complex (MHC) class I genes has been studied in two cell clones (B9 and G2) of the methylcholanthrene-induced murine fibrosarcoma GR9. These two clones were selected based on their different biological and biochemical behavior specially related to their tumor induction capability when injected into a BALB/c mouse. t-BOOH (0.125 mM) induced the expression of H-2 molecules in both cell clones. In B9 cell clone, in which MHC basal expression is very low or absent, t-BOOH significantly induced H-2Kd, H-2Dd and H-2Ld molecules. In G2 cell clone the expression of MHC class I genes was also enhanced by the xenobiotic, the effect being especially significant on the H-2Ld molecule which is not expressed under basal conditions. H-2 molecules expression was accompanied by the activation of the transactivator factor NF kappa B. These results suggest that oxidative stress may modulate the antigen expression of tumor cells and thus the immune response of the host organism. Basal levels of oxidative parameters, such as anti-oxidant enzymes, malondialdehyde (MDA) and the DNA damaged base 8-hydroxy-2'-deoxyguanosine (8-OHdG), showed differences between the two fibrosarcoma cell clones.

3T3 Cells↗
PubMed1994

Neural-immunologic interactions in asthma.

Recent investigations offer insights into the possible cause of asthma: Rather than being due to either neural or immunologic events, the fault may lie in concurrent malfunctioning of two interacting systems. Antigenic stimulation, for example, can affect neural depolarization and firing; by the same token, nerve stimulation can affect the growth and function of inflammatory cells.

Animals↗
PubMed1994

Extracellular Ca2+ modulates leukocyte function-associated antigen-1 cell surface distribution on T lymphocytes and consequently affects cell adhesion.

Transition of leukocyte function-associated antigen-1 (LFA-1), from an inactive into an activate state depends on the presence of extracellular Mg2+ and/or Ca2+ ions. Although Mg2+ is directly involved in ligand binding, the role of Ca2+ in LFA-1 mediated adhesion remained obscure. We now demonstrate that binding of Ca2+, but not Mg2+, directly correlates with clustering of LFA-1 molecules at the cell surface of T cells, thereby facilitating LFA-1-ligand interaction. Using a reporter antibody (NKI-L16) that recognizes a Ca(2+)-dependent epitope on LFA-1, we found that Ca2+ can be bound by LFA-1 with different strength. We noticed that weak binding of Ca2+ is associated with a dispersed LFA-1 surface distribution on T cells and with non-responsiveness of these cells to stimuli known to activate LFA-1. In contrast, stable binding of Ca2+ by LFA-1 correlates with a patch-like surface distribution and vivid ligand binding after activation of LFA-1. Mg(2+)-dependent ligand binding does not affect binding of Ca2+ by LFA-1 as measured by NKI-L16 expression, suggesting that Mg2+ binds to a distinct site, and that both cations are important to mediate adhesion. Only Sr2+ ions can replace Ca2+ to express the L16 epitope, and to induce clustering of LFA-1 at the cell surface. We conclude that Ca2+ is involved in avidity regulation of LFA-1 by clustering of LFA-1 molecules at the cell surface, whereas Mg2+ is important in regulation of the affinity of LFA-1 for its ligands.

Calcium↗
PubMed1984

Modulation of T cell differentiation, antigen expression, and radiosensitivity of suppressor cells during late phases of graft-versus-host reactivity.

Suppressor cells generated by inoculation of (B10 X B10.A)F1 hybrid mice with parental spleen cells were characterized during the late period of graft-versus-host (GVH) reactivity, starting on day 14 after parental spleen cell injection and continuing until loss of suppressor activity. The suppressor cell potential was assessed by the ability of spleen cells from the injected F1 mice to suppress the generation of allogeneic cytotoxic T lymphocyte (CTL) responses in vitro by normal F1 responder cells. GVH-associated suppression could be abrogated by anti-Lyt 1, anti-Lyt 2, and anti-Thy 1 plus complement (C') before day 7 postinoculation, and by anti-Lyt 2 and anti-Thy 1 thereafter. However, from day 14 postinoculation on, suppressor cells were insensitive to either of these antibodies. This phase was associated with strong suppressor potential. Subsequent to this period suppressor cells were again sensitive to anti-Thy 1, but not to anti-Lyt 1 or anti-Lyt 2 plus C'--and at the same time they decreased in suppressor activity. Moreover, during the period of resistance to anti-T-cell antibodies plus C', suppressor cells were not killed by anti-asialo GM1 plus C'; were nonadherent to Sephadex G10, and were enriched by nylon-wool passage. In the course of GVH reactivity, suppressor cells alternated in sensitivity and resistance to 500 rads and once went through a brief period of resistance to 2000 rads that was associated with strong suppression and occasionally with mortality. The kinetics of these changes in cell surface phenotype and radiosensitivity were found to vary, coinciding with the strength of the suppression, but the sequence of these events was always the same. During the entire period of GVH reactivity, suppression was mediated by parental cells.

Animals↗
PubMed1992

Modulation of hepatitis B viral antigen expression by immunosuppressive drugs in primary hepatocyte culture.

In one pattern of hepatitis B virus (HBV) recurrence following orthotopic liver transplantation--namely, fibrosing cholestatic hepatitis (FCH), the intrahepatic expression of HBV antigens was found to be markedly increased, suggesting that HBV may be directly cytopathic to the liver cells. Understanding how immunosuppressive drugs influence HBV may be of considerable clinical relevance in the treatment of patients with chronic HBV infection after liver transplantation. To determine how these drugs influence intrahepatic HBV antigen expression, hepatocytes isolated from patients with chronic HBV infection were incubated in the absence or presence of prednisolone (10(-6)-10(-10) M), methylprednisolone (10(-6)-10(-10) M), azathioprine (0.1-10 micrograms/ml), or cyclosporine (50-1000 ng/ml) and the amount of intracellular/secreted antigen was measured by radioimmunoassay. Intracellular HBsAg increased by 25.0-51.1% with prednisolone 10(-8)-10(-6) M (n = 14, P less than 0.05) and methylprednisolone 10(-9)-10(-6) M (n = 8, P less than 0.05). Immunocytochemistry of cytospins showed that the proportion of cells containing HBsAg increased by 20-38% with stronger staining, but the distribution of HBsAg remained diffusely cytoplasmic; the changes in intracellular pre-S1 and pre-S2 paralleled those of HBsAg. Secreted HBsAg was, however, not affected. There was also an increase in intracellular nucleocapsid antigens by 24.1-32.5% with an increase in hepatocytes containing nucleocapsid antigens by 8-18%. Methylprednisolone exerted similar effects to prednisolone. On the other hand, neither azathioprine (n = 11) nor cyclosporine (n = 12) had any effect on intracellular or secreted HBsAg or nucleocapsid antigens. These data indicate that corticosteroids, but not azathioprine or cyclosporine, enhance intracellular HBV antigen expression in this short-term culture system. This may be an important factor in the evolution of FCH and careful attention to the use of corticosteroids may be beneficial in patients with chronic HBV infection undergoing liver transplantation.

Adult↗
PubMed1994

Prolongation of in vivo mouse islet allograft survival by modulation of MHC class I antigen.

Major histocompatibility complex class I-deficient islets from beta-2 microglobulin-deficient mice have been shown to have prolonged in vivo islet allograft survival. Additionally in vitro studies using the mixed lymphocyte islet coculture system have demonstrated a reduction in cytotoxic T lymphocyte activity against alloislets that have been pretreated with an antibody directed against MHC class I antigen. The clinical applicability of these findings are examined in this study, which evaluates the ability of MHC class I blocking antibody to prevent the in vivo destruction of alloislets. Recipients of allogenic islet transplants treated with phosphate-buffered saline or control F(ab')2 fragments rejected the transplanted alloislets in median times of 11.5 days and 11 days, respectively. Recipient mice treated with a monoclonal antibody or F(ab')2 fragments specific to the donor MHC class I antigen had significant prolongation in allograft survival (median allograft survival for both groups was 21 days) when compared with mice treated with PBS or control F(ab')2 fragment. These results demonstrate that treating recipients of alloislets with donor-specific MHC class I monoclonal antibody or the respective F(ab')2 fragments prolongs islet allograft survival. This confirms the importance of MHC class I antigen in the rejection of pancreatic islet allografts and suggests that blocking different domains on the MHC class I molecule could be used therapeutically in the protection of allografts from the immune system.

Animals↗
PubMed1995

Interferon-gamma-dependent stimulation of Fas antigen in SV40-transformed human keratinocytes: modulation of the apoptotic process by protein kinase C.

Fas antigen is a cell membrane protein that has been suggested to mediate apoptosis. Using SV40-transformed human keratinocytes, we investigated the Fas-antigen-dependent apoptotic process. The expression of Fas antigen mRNA was markedly induced by interferon-gamma (IFN-gamma) treatment (500 U/ml). After IFN-gamma treatment in the presence of anti-Fas monoclonal antibody, apoptosis was induced, as detected by the formation of nucleosome-sized fragments of DNA and morphologically by apoptotic cells with round homogeneous nuclear beads detected by acridine orange staining. The apoptotic SV40-transformed keratinocytes were analyzed quantitatively by enzyme-linked immunosorbent assay using antihistone and peroxidase-conjugated anti-DNA antibodies to detect cell death. The IFN-gamma- and anti-Fas antibody-dependent apoptotis was observed by 3 h, and the maximal response was observed by 12 h. The induction of apoptosis was significantly augmented by treatment with 10 ng/ml 12-o-tetradecanoyl-phorbol-13-acetate (TPA). TPA alone had no effect on either Fas antigen expression or on the apoptotic process. Other protein kinase C activators (1-oleoyl-2-acetylglycerol and mezerein) also stimulated IFN-gamma-dependent apoptosis, whereas 4-o-methyl phorbol myristate acetate, a very weak protein kinase C activator, had only a slight effect. The TPA-induced augmentation of apoptosis was inhibited by the protein kinase C inhibitor, 1-(5-isoquinoline-sulfonyl)-2-methyl piperazine dihydrochloride (H-7). However, H-7 inhibited only the TPA-induced augmentation of apoptosis; the basal IFN-gamma- and anti-Fas-dependent apoptosis remained in the presence of H-7. Northern blot analysis revealed that c-jun mRNA was induced by IFN-gamma plus anti-Fas antibody treatment as well as by TPA treatment; the addition of IFN-gamma alone to the incubation medium had no effect on the expression of c-jun mRNA. These results indicate that IFN-gamma induces a Fas-antigen-dependent apoptotic process in SV40-transformed keratinocytes and that TPA augments the process through the activation of protein kinase C.

Apoptosis↗
PubMed2006

Functional signatures of protective antiviral T-cell immunity in human virus infections.

The most common human viruses have different abilities to establish persistent chronic infection. Virus-specific T-cell responses are critical in the control of virus replication and in the prevention of disease in chronic infection. A large number of phenotypic markers and a series of functions have been used to characterize virus-specific CD4+ and CD8+ T-cell responses, and these studies have shown great phenotypic and functional heterogeneity of the T-cell responses against different viruses. The heterogeneity of the T-cell response has been proposed to be specific to each virus. However, over the past 2 years, several studies have provided evidence that the phenotypic and functional heterogeneity of CD4+ and CD8+ T-cell responses is predominantly regulated by the levels of antigen load. The levels of antigen load modulate the phenotypic and functional patterns of the T-cell response within the same virus infection. Furthermore, the functional characterization of virus-specific CD4+ and CD8+ T-cell responses has identified signatures of protective antiviral immunity. Polyfunctional, i.e. interleukin-2 and interferon-gamma (IFN-gamma) secretion and proliferation, and not monofunctional, i.e. IFN-gamma secretion, CD4+ and CD8+ T-cell responses represent correlates of protective antiviral immunity in chronic virus infections.

Acute Disease↗
PubMed1991

Intravenous immunoglobulins (IVIg) in the treatment of autoimmune diseases.

Intravenous immunoglobulin (IVIg) therapy is increasingly used in autoimmune diseases. Although its efficacy has only been established in a few specific antibody-mediated autoimmune conditions, accumulating evidence on the regulatory role of circulating immunoglobulins in the selection of peripheral B cell repertoires makes it an attractive potential therapeutic option to clinical immunologists. This overview briefly discusses the current use of IVIg in human autoimmune diseases with a particular emphasis on the possible mechanisms by which IVIg could suppress pathological autoimmune responses.

Antigenic Modulation↗