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Full-Text Articles in Life Sciences
Viral Replication And Paracrine Effects Result In Distinct, Functional Responses Of Dendritic Cells Following Infection With Dengue 2 Virus, Zachary Nightingale, Chinmay Patkar, Alan Rothman
Viral Replication And Paracrine Effects Result In Distinct, Functional Responses Of Dendritic Cells Following Infection With Dengue 2 Virus, Zachary Nightingale, Chinmay Patkar, Alan Rothman
Alan Rothman
Dengue virus (DENV), a re-emerging arbovirus, readily infects dendritic cells (DC) in culture and in vivo. However, there have been contradictory reports regarding the effect of DENV infection on DC activation and maturation. DC undergo a series of functional changes following exposure to infectious agents, including cytokine production and costimulatory and MHC molecule induction, culminating in stimulation of adaptive immune responses. Immunological memory to primary DENV infection critically influences disease severity during subsequent infections with heterologous serotypes. To explore these phenomena, we examined DENV infection-dependent and -independent effects on DC secretory, phenotypic, and allostimulatory functions. DENV infection of DC resulted …
Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman
Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman
Alan Rothman
Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by …
Intracellular Cytokine Production By Dengue Virus-Specific T Cells Correlates With Subclinical Secondary Infection, Steven Hatch, Timothy Endy, Stephen Thomas, Anuja Mathew, James Potts, Pamela Pazoles, Daniel Libraty, Robert Gibbons, Alan Rothman
Intracellular Cytokine Production By Dengue Virus-Specific T Cells Correlates With Subclinical Secondary Infection, Steven Hatch, Timothy Endy, Stephen Thomas, Anuja Mathew, James Potts, Pamela Pazoles, Daniel Libraty, Robert Gibbons, Alan Rothman
Alan Rothman
The pathophysiology of dengue virus infection remains poorly understood, although secondary infection is strongly associated with more severe disease. In the present study, we performed a nested, case-control study comparing the responses of pre-illness peripheral blood mononuclear cells between children who would subsequently develop either subclinical or symptomatic secondary infection 6-11 months after the baseline blood samples were obtained and frozen. We analyzed intracellular cytokine production by CD4(+) and CD8(+) cells in response to stimulation with dengue antigen. We found higher frequencies of dengue virus-specific TNFalpha, IFNgamma-, and IL-2-producing T cells among schoolchildren who subsequently developed subclinical infection, compared with …
T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman
T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman
Alan Rothman
Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF …
Cross-Subtype Antibody And Cellular Immune Responses Induced By A Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccine In Healthy Human Volunteers, Shixia Wang, Jeffrey Kennedy, Kim West, David Montefiori, Scott Coley, John Lawrence, Siyuan Shen, Sharone Green, Alan Rothman, Francis Ennis, James Arthos, Ranajit Pal, Phillip Markham, Shan Lu
Cross-Subtype Antibody And Cellular Immune Responses Induced By A Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccine In Healthy Human Volunteers, Shixia Wang, Jeffrey Kennedy, Kim West, David Montefiori, Scott Coley, John Lawrence, Siyuan Shen, Sharone Green, Alan Rothman, Francis Ennis, James Arthos, Ranajit Pal, Phillip Markham, Shan Lu
Alan Rothman
An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNgamma ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 …
Transient Decreases In Human T Cell Proliferative Responses Following Vaccinia Immunization, Anuja Mathew, Francis Ennis, Alan Rothman
Transient Decreases In Human T Cell Proliferative Responses Following Vaccinia Immunization, Anuja Mathew, Francis Ennis, Alan Rothman
Alan Rothman
To further study the immunosuppression associated with virus infections, we analyzed the proliferative responses of serial PBMC samples obtained following vaccinia virus immunization. In four of five volunteers, responses to PHA, anti-CD3, vaccinia virus, and recall antigens were markedly decreased at at least one time point between days 5 and 29 after vaccination. Responses to PHA were restored by the addition of IL-2 or irradiated autologous healthy PBMC in the two volunteers tested, suggesting that the proliferation defect is attributable to accessory cell dysfunction. In one donor, immobilized anti-CD3 failed to induce proliferation, but addition of immobilized anti-CD28 partially restored …
Discordance Between Antibody And T Cell Responses In Recipients Of Trivalent Inactivated Influenza Vaccine, Mary Co, Laura Orphin, John Cruz, Pamela Pazoles, Alan Rothman, Francis Ennis, Masanori Terajima
Discordance Between Antibody And T Cell Responses In Recipients Of Trivalent Inactivated Influenza Vaccine, Mary Co, Laura Orphin, John Cruz, Pamela Pazoles, Alan Rothman, Francis Ennis, Masanori Terajima
Alan Rothman
Thirty adults were tested for humoral and cellular immune responses following immunization with the trivalent inactivated influenza vaccine. Modest but significant inverse correlations between the baseline and the fold changes in the number of IFNgamma-producing cells and the levels of neutralizing antibodies were observed. Specific increases in proliferative responses in the CD8 CD45RA+ population were noted after vaccination. Minimal correlations between neutralizing antibody titers and the number of IFNgamma-producing cells in terms of prevaccination levels or fold increases were observed. These results show specific increases in a CD8 T cell subset and discordant T and B responses induced by the …
Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman
Impaired T Cell Proliferation In Acute Dengue Infection, Anuja Mathew, Ichiro Kurane, Sharone Green, David Vaughn, Siripen Kalayanarooj, Saroj Suntayakorn, Francis Ennis, Alan Rothman
Sharone Green
Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by …
T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman
T Cell Responses To An Hla-B*07-Restricted Epitope On The Dengue Ns3 Protein Correlate With Disease Severity, Iva Zivna, Sharone Green, David Vaughn, Siripen Kalayanarooj, Henry Stephens, Dasnayanee Chandanayingyong, Ananda Nisalak, Francis Ennis, Alan Rothman
Sharone Green
Dengue hemorrhagic fever (DHF), the severe manifestation of dengue virus (DV) infection characterized by plasma leakage, is more common in secondary DV infections in previously infected individuals and is associated with high levels of immune activation. To determine the Ag specificity of this immune response, we studied the response to an HLA-B*07-restricted T cell epitope, residues 221-232 of the DV NS3 protein, in 10 HLA-B*07(+) Thai children who were studied during and after acute DV infections. Peptide-specific T cells were detected in 9 of 10 subjects. The frequency of peptide-specific T cells was higher in subjects who had experienced DHF …
Cross-Subtype Antibody And Cellular Immune Responses Induced By A Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccine In Healthy Human Volunteers, Shixia Wang, Jeffrey Kennedy, Kim West, David Montefiori, Scott Coley, John Lawrence, Siyuan Shen, Sharone Green, Alan Rothman, Francis Ennis, James Arthos, Ranajit Pal, Phillip Markham, Shan Lu
Cross-Subtype Antibody And Cellular Immune Responses Induced By A Polyvalent Dna Prime-Protein Boost Hiv-1 Vaccine In Healthy Human Volunteers, Shixia Wang, Jeffrey Kennedy, Kim West, David Montefiori, Scott Coley, John Lawrence, Siyuan Shen, Sharone Green, Alan Rothman, Francis Ennis, James Arthos, Ranajit Pal, Phillip Markham, Shan Lu
Sharone Green
An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report on the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6-001, in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNgamma ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 …
Chop Mediates Endoplasmic Reticulum Stress-Induced Apoptosis In Gimap5-Deficient T Cells, Steven Pino, Bryan O'Sullivan-Murphy, Erich Lidstone, Chaoxing Yang, Kathryn Lipson, Agata Jurczyk, Philip Diiorio, Michael Brehm, John Mordes, Dale Greiner, Aldo Rossini, Rita Bortell
Chop Mediates Endoplasmic Reticulum Stress-Induced Apoptosis In Gimap5-Deficient T Cells, Steven Pino, Bryan O'Sullivan-Murphy, Erich Lidstone, Chaoxing Yang, Kathryn Lipson, Agata Jurczyk, Philip Diiorio, Michael Brehm, John Mordes, Dale Greiner, Aldo Rossini, Rita Bortell
Philip J diIorio Jr
Gimap5 (GTPase of the immunity-associated protein 5) has been linked to the regulation of T cell survival, and polymorphisms in the human GIMAP5 gene associate with autoimmune disorders. The BioBreeding diabetes-prone (BBDP) rat has a mutation in the Gimap5 gene that leads to spontaneous apoptosis of peripheral T cells by an unknown mechanism. Because Gimap5 localizes to the endoplasmic reticulum (ER), we hypothesized that absence of functional Gimap5 protein initiates T cell death through disruptions in ER homeostasis. We observed increases in ER stress-associated chaperones in T cells but not thymocytes or B cells from Gimap5(-/-) BBDP rats. We then …
Tacrolimus And Cyclosporine A Inhibit Allostimulatory Capacity And Cytokine Production Of Human Myeloid Dendritic Cells, Gyongyi Szabo, C. Gavala, Pranoti Mandrekar
Tacrolimus And Cyclosporine A Inhibit Allostimulatory Capacity And Cytokine Production Of Human Myeloid Dendritic Cells, Gyongyi Szabo, C. Gavala, Pranoti Mandrekar
Gyongyi Szabo
Myeloid dendritic cells (DCs) are pivotal in the recognition of alloantigens and, therefore, in the induction of allograft rejection. Induction of alloreactive T cell proliferation by myeloid DCs depends on the maturation of DCs, the expression of costimulatory molecules, and the cytokine environment. This study investigated the effects of tacrolimus and cyclosporine A (CsA) on DC maturation and allostimulatory capacity. Myeloid DCs were propagated from normal blood monocytes with interleukin (IL) 4 and GM-CSF for 7 days in the presence or absence of tacrolimus (FK506; 10 nM) or CsA (1 microg/mL). Exposure of DCs during maturation to tacrolimus or CsA …
Reduced Alloreactive T-Cell Activation After Alcohol Intake Is Due To Impaired Monocyte Accessory Cell Function And Correlates With Elevated Il-10, Il-13, And Decreased Ifngamma Levels, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc, Donna Catalano, Karen Kodys
Reduced Alloreactive T-Cell Activation After Alcohol Intake Is Due To Impaired Monocyte Accessory Cell Function And Correlates With Elevated Il-10, Il-13, And Decreased Ifngamma Levels, Gyongyi Szabo, Pranoti Mandrekar, Angela Dolganiuc, Donna Catalano, Karen Kodys
Gyongyi Szabo
BACKGROUND: Immunosuppression associated with chronic alcohol use is characterized by reduced antigen-specific T-cell response and impaired delayed type hypersensitivity. Increasing evidence suggests in chronic alcohol consumption models that reduced antigen-specific T-cell proliferation is due to insufficient accessory cell function. Accessory cell function, a critical step in recognition of viral antigens, is reduced in chronic hepatitis C. The severity of hepatitis C is increased by alcohol consumption. Thus, we investigated the effects of alcohol consumption on accessory cell activity of monocytes in supporting alloreactive T-cell proliferation. METHODS: Alloreactive T-cell proliferation was evaluated in a one-way mixed lymphocyte reaction (MLR). Mononuclear cells …
Human Macrophages Degrade Tryptophan Upon Induction By Interferon-Gamma, Ernst Werner, Gabriele Bitterlich, Dietmar Fuchs, Arno Hausen, Gilbert Reibnegger, Gyongyi Szabo, Manfred Dierich, Helmut Wachter
Human Macrophages Degrade Tryptophan Upon Induction By Interferon-Gamma, Ernst Werner, Gabriele Bitterlich, Dietmar Fuchs, Arno Hausen, Gilbert Reibnegger, Gyongyi Szabo, Manfred Dierich, Helmut Wachter
Gyongyi Szabo
Human peripheral blood mononuclear cells, monocytes-macrophages and T-cells were stimulated with human recombinant interferon-gamma, interferon-alpha and phytohemagglutinin. The culture supernatants were analyzed for tryptophan, kynurenine, 3-hydroxyanthranilic acid, anthranilic acid and neopterin by high performance liquid chromatography. Tryptophan was decreased and the four other compounds were increased in supernatants of peripheral blood mononuclear cells activated by interferon-gamma (250 U/ml), interferon-alpha (10.000 U/ml) and phytohemagglutinin (1 microgram/ml). After splitting of peripheral blood mononuclear cells by adherence, the monocytes and macrophages but not the T-cells degraded tryptophan upon stimulation by interferon-gamma in a dose dependent manner. Supernatants of phytohemagglutinin stimulated but not of …
Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar
Ethanol-Mediated Regulation Of Transcription Factors In Immunocompetent Cells, Gyongyi Szabo, Pranoti Mandrekar
Gyongyi Szabo
The immunomodulatory effects of acute and chronic alcohol use are characterized by impaired antigen-specific immune activation and by increased susceptibility to infections due to alterations in innate immune responses and inflammatory mediator production. The central feature of cellular responses to inflammatory and stress signals is the activation of the nuclear regulatory kappa B/Rel family of transcriptional factors via various surface receptor systems in immunocompetent cells. Activation of NF-kappa B, however, is regulated at multiple levels including I-kappa B degradation, nuclear translocation, and by interaction of NF-kappa B/Rel with other transcription factors. Data from our and other laboratories demonstrate that acute …
Antigen Presentation By The Cd4 Positive Monocyte Subset, Gyongyi Szabo, Carol Miller-Graziano, Karen Kodys
Antigen Presentation By The Cd4 Positive Monocyte Subset, Gyongyi Szabo, Carol Miller-Graziano, Karen Kodys
Gyongyi Szabo
Although CD4 antigen is expressed on monocytes (MO), its functional role is uncharacterized. In this study, isolated human MO were separated into CD4+ and CD4- MO subsets and assessed for presentation of tetanus toxoid. The CD4- MO subset had decreased antigen presenting cell (APC) capacity as well as increased PGE2 production when compared to the CD4+ MO subset. Addition of a cyclo-oxygenase inhibitor (Indomethacin) did not restore the CD4- MO subset's APC capacity to that of the similarly treated CD4+ MO subset, eliminating differential PGE2 production as the primary cause of differential APC capacity. Production of monokines such as IL-1 …
Selective Inhibition Of Antigen-Specific T Lymphocyte Proliferation By Acute Ethanol Exposure: The Role Of Impaired Monocyte Antigen Presentation Capacity And Mediator Production, Gyongyi Szabo, Bikash Verma, Donna Catalano
Selective Inhibition Of Antigen-Specific T Lymphocyte Proliferation By Acute Ethanol Exposure: The Role Of Impaired Monocyte Antigen Presentation Capacity And Mediator Production, Gyongyi Szabo, Bikash Verma, Donna Catalano
Gyongyi Szabo
Ethanol consumption is associated with impaired immunity. Our data demonstrate that even a single dose of a biologically relevant concentration (25-150 mM) of ethanol can down-regulate antigen-specific T lymphocyte proliferation. In contrast, ethanol augmented mitogen-induced T cell proliferation, suggesting that its inhibitory effect on antigen-specific T cell proliferation was due to its effects on monocytes (m phi s) rather than on T cells. The immunodepressive effects of ethanol on m phi antigen-presenting cell (APC) capacity were manifested whether alcohol treatment was limited to the antigen uptake-processing period only or was present during the entire period of antigen presentation. These inhibitory …
Inhibition Of Superantigen-Induced T Cell Proliferation And Monocyte Il-1 Beta, Tnf-Alpha, And Il-6 Production By Acute Ethanol Treatment, Gyongyi Szabo, Pranoti Mandrekar, Donna Catalano
Inhibition Of Superantigen-Induced T Cell Proliferation And Monocyte Il-1 Beta, Tnf-Alpha, And Il-6 Production By Acute Ethanol Treatment, Gyongyi Szabo, Pranoti Mandrekar, Donna Catalano
Gyongyi Szabo
Alcohol use has been shown to decrease monocyte antigen presentation capacity and inflammatory cytokine production, thereby increasing susceptibility to infections. Here, we demonstrate that in vitro acute treatment of normal monocytes with pharmacological doses of ethanol can decrease superantigen [Staphylococcus enterotoxins B (SEB) and A (SEA)]-induced T cell proliferation. Furthermore, ethanol treatment (25-100 mM) significantly inhibited SEA- or SEB-induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in monocytes. Ethanol-induced down-regulation of monocyte TNF-alpha, IL-1 beta, and IL-6 occurred at both the protein and mRNA levels. Additional data suggest that ethanol can decrease IL-1 beta mRNA …
Hepatitis C And Innate Immunity: Recent Advances, Gyongyi Szabo, Angela Dolganiuc
Hepatitis C And Innate Immunity: Recent Advances, Gyongyi Szabo, Angela Dolganiuc
Gyongyi Szabo
Eradication of hepatitis C virus (HCV) infection requires a complex and coordinated interplay between innate and adaptive immune responses that, when it fails, leads to chronic infection. In this review, the innate immune mechanisms by which HCV is sensed and by which HCV undermines host defense are discussed. The critical role of dendritic cells in antigen presentation and T-cell activation in addition to type I interferon production and interference of HCV with innate immune cell functions are reviewed. Finally, current and emerging therapeutic approaches targeting innate immune pathways are evaluated.
Inhibition Of Myeloid Dendritic Cell Accessory Cell Function And Induction Of T Cell Anergy By Alcohol Correlates With Decreased Il-12 Production, Pranoti Mandrekar, Donna Catalano, Angela Dolganiuc, Karen Kodys, Gyongyi Szabo
Inhibition Of Myeloid Dendritic Cell Accessory Cell Function And Induction Of T Cell Anergy By Alcohol Correlates With Decreased Il-12 Production, Pranoti Mandrekar, Donna Catalano, Angela Dolganiuc, Karen Kodys, Gyongyi Szabo
Gyongyi Szabo
Alcohol consumption inhibits accessory cell function and Ag-specific T cell responses. Myeloid dendritic cells (DCs) coordinate innate immune responses and T cell activation. In this report, we found that in vivo moderate alcohol intake (0.8 g/kg of body weight) in normal volunteers inhibited DC allostimulatory capacity. Furthermore, in vitro alcohol treatment during DC differentiation significantly reduced allostimulatory activity in a MLR using naive CD4(+) T cells, and inhibited tetanus toxoid Ag presentation by DCs. Alcohol-treated DCs showed reduced IL-12, increased IL-10 production, and a decrease in expression of the costimulatory molecules CD80 and CD86. Addition of exogenous IL-12 and IL-2, …