scholarly journals Influenza Virus Vaccination Induces Interleukin-12/23 Receptor β1 (IL-12/23Rβ1)-Independent Production of Gamma Interferon (IFN-γ) and Humoral Immunity in Patients with Genetic Deficiencies in IL-12/23Rβ1 or IFN-γ Receptor I

2008 ◽  
Vol 15 (8) ◽  
pp. 1171-1175 ◽  
Author(s):  
Tjitske de Boer ◽  
Jaap T. van Dissel ◽  
Taco W. J. Kuijpers ◽  
Guus F. Rimmelzwaan ◽  
Frank P. Kroon ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Seasonal Influenza ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Virus Vaccination ◽  
Cell Responses ◽  
Antibody Titers ◽  
Ifn Γ ◽  
Striking Contrast

ABSTRACT To investigate whether protective immune responses can be induced in the absence of normal interleukin-12/23/gamma interferon (IL-12/23/IFN-γ) axis signaling, we vaccinated with the seasonal influenza virus subunit vaccine two patients with complete IL-12/23 receptor β1 (IL-12/23Rβ1) deficiencies, two patients with partial IFN-γ receptor I (pIFN-γRI) deficiencies, and five healthy controls. Blood samples were analyzed before, 7 days after, and 28 days after vaccination. In most cases, antibody titers reached protective levels. Moreover, although T-cell responses in patients were lower than those observed in controls, significant influenza virus-specific T-cell proliferation, IFN-γ production, and numbers of IFN-γ-producing cells were found in all patients 7 days after the vaccination. Interestingly, influenza virus-specific IFN-γ responses were IL-12/23 independent, in striking contrast to mycobacterium-induced IFN-γ production. In conclusion, influenza virus vaccination induces IL-12/23-independent IFN-γ production by T cells and can result in sufficient humoral protection in both IL-12/23Rβ1- and pIFN-γRI-deficient individuals.

scholarly journals Modulation of an Interleukin-12 and Gamma Interferon Synergistic Feedback Regulatory Cycle of T-Cell and Monocyte Cocultures by Porphyromonas gingivalis Lipopolysaccharide in the Absence or Presence of Cysteine Proteinases

2002 ◽  
Vol 70 (10) ◽  
pp. 5695-5705 ◽  
Author(s):  
Peter L. W. Yun ◽  
Arthur A. DeCarlo ◽  
Charles Collyer ◽  
Neil Hunter
Keyword(s):  
T Cells ◽  
T Cell ◽  
Porphyromonas Gingivalis ◽  
Gamma Interferon ◽  
Periodontal Pathogen ◽  
Interleukin 12 ◽  
Minor Role ◽  
Cysteine Proteinases ◽  
Activated T Cells ◽  
Ifn Γ

ABSTRACT Interleukin 12 (IL-12) is an efficient inducer and enhancer of gamma interferon (IFN-γ) production by both resting and activated T cells. There is evidence that human monocytes exposed to IFN-γ have enhanced ability to produce IL-12 when stimulated with lipopolysaccharide (LPS). In this study, it was demonstrated that LPS from the oral periodontal pathogen Porphyromonas gingivalis stimulated monocytes primed with IFN-γ to release IL-12, thereby enhancing IFN-γ accumulation in T-cell populations. P. gingivalis LPS was shown to enhance IL-12 induction of IFN-γ in T cells in a manner independent from TNF-α contribution. The levels of T-cell IL-12 receptors were not affected by P. gingivalis LPS and played only a minor role in the magnitude of the IFN-γ response. These data suggest that LPS from P. gingivalis establishes an activation loop with IL-12 and IFN-γ with potential to augment the production of inflammatory cytokines in relation to the immunopathology of periodontitis. We previously reported that the major cysteine proteinases (gingipains) copurifying with LPS in this organism were responsible for reduced IFN-γ accumulation in the presence of IL-12. However, the addition of the gingipains in the presence of LPS resulted in partial restoration of the IFN-γ levels. In the destructive periodontitis lesion, release of gingipains from the outer membrane (OM) of P. gingivalis could lead to the downregulation of Th1 responses, while gingipain associated with LPS in the OM or in OM vesicles released from the organism could have net stimulatory effects.

scholarly journals Boosted Influenza-Specific T Cell Responses after H5N1 Pandemic Live Attenuated Influenza Virus Vaccination

2015 ◽  
Vol 6 ◽  
Author(s):  
YanChun Peng ◽  
Beibei Wang ◽  
Kawsar Talaat ◽  
Ruth Karron ◽  
Timothy J. Powell ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
T Cell Responses ◽  
Virus Vaccination ◽  
Cell Responses ◽  
Live Attenuated Influenza Virus

scholarly journals Rapid Development of a Gamma Interferon-Secreting Glycolipid/CD1d-Specific Vα14+ NK1.1− T-Cell Subset after Bacterial Infection

2006 ◽  
Vol 74 (10) ◽  
pp. 5903-5913 ◽  
Author(s):  
Masashi Emoto ◽  
Izumi Yoshizawa ◽  
Yoshiko Emoto ◽  
Mamiko Miamoto ◽  
Robert Hurwitz ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Bacterial Infection ◽  
Rapid Development ◽  
Cell Subset ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
T Cell Subset ◽  
Early Stages ◽  
Ifn Γ

ABSTRACT The phenotypic and functional changes of glycolipid presented by CD1d(glycolipid/CD1d) specific Vα14+ T cells in the liver of mice at early stages of bacterial infection were investigated. After Listeria monocytogenes infection or interleukin-12 (IL-12) treatment, α-galactosylceramide/CD1d tetramer-reactive (α-GalCer/CD1d+) T cells coexpressing natural killer (NK) 1.1 marker became undetectable and, concomitantly, cells lacking NK1.1 emerged in both euthymic and thymectomized animals. Depletion of the NK1.1+ subpopulation prevented the emergence of α-GalCer/CD1d+ NK1.1− T cells. Before infection, NK1.1+, rather than NK1.1−, α-GalCer/CD1d+ T cells coexpressing CD4 were responsible for IL-4 production, whereas gamma interferon (IFN-γ) was produced by cells regardless of NK1.1 or CD4 expression. After infection, IL-4-secreting cells became undetectable among α-GalCer/CD1d+ T cells, but considerable numbers of IFN-γ-secreting cells were found among NK1.1−, but not NK1.1+, cells lacking CD4. Thus, NK1.1 surface expression and functional activities of Vα14+ T cells underwent dramatic changes at early stages of listeriosis, and these alterations progressed in a thymus-independent manner. In mutant mice lacking all α-GalCer/CD1d+ T cells listeriosis was ameliorated, suggesting that the subtle contribution of the NK1.1− T-cell subset to antibacterial protection is covered by more profound detrimental effects of the NK1.1+ T-cell subset.

scholarly journals The Early Kinetics of Cytomegalovirus-Specific CD8+ T-Cell Responses Are Not Affected by Antigen Load or the Absence of Perforin or Gamma Interferon

2008 ◽  
Vol 82 (10) ◽  
pp. 4931-4937 ◽  
Author(s):  
Daniel M. Andrews ◽  
Christopher E. Andoniou ◽  
Peter Fleming ◽  
Mark J. Smyth ◽  
Mariapia A. Degli-Esposti
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
T Cell Responses ◽  
Gamma Interferon ◽  
Murine Cytomegalovirus ◽  
Cell Responses ◽  
Ifn Γ ◽  
T Cell Expansion ◽  
Kinetics Of

ABSTRACT Both innate and adaptive immune responses participate in the control of murine cytomegalovirus (mCMV) infection. In some mouse strains, like BALB/c, the control of infection relies on the activities of CD8+ T cells. mCMV-specific CD8+ T-cell responses are unusual in that, even after mCMV has been controlled in the periphery, the numbers of circulating virus-specific CD8+ T cells remain high compared to those observed in other viral infections. To better understand the generation and maintenance of mCMV-specific CD8+ T-cell responses, we evaluated how antigen load and effector molecules, such as perforin (Prf) and gamma interferon (IFN-γ), influence these responses during acute infection in vivo. Viral burden affected the magnitude, but not the early kinetics, of antigen-specific CD8+ T-cell responses. Similarly, the magnitude of virus-specific CD8+ T-cell expansion was affected by Prf and IFN-γ, but contraction of antigen-specific responses occurred normally in both Prf- and IFN-γ-deficient mice. These data indicate that control of mCMV-specific CD8+ T-cell expansion and contraction is more complex than anticipated and, despite the role of Prf or IFN-γ in controlling viral replication, a full program of T-cell expansion and contraction can occur in their absence.

scholarly journals Assessment of Seasonal Influenza A Virus-Specific CD4 T-Cell Responses to 2009 Pandemic H1N1 Swine-Origin Influenza A Virus

2010 ◽  
Vol 84 (7) ◽  
pp. 3312-3319 ◽  
Author(s):  
Xinhui Ge ◽  
Venus Tan ◽  
Paul L. Bollyky ◽  
Nathan E. Standifer ◽  
Eddie A. James ◽  
...  
Keyword(s):  
T Cells ◽  
Influenza Virus ◽  
Amino Acid ◽  
T Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Seasonal Influenza ◽  
T Cell Responses ◽  
Pandemic H1n1 ◽  
Cell Responses

ABSTRACT Very limited evidence has been reported to show human adaptive immune responses to the 2009 pandemic H1N1 swine-origin influenza A virus (S-OIV). We studied 17 S-OIV peptides homologous to immunodominant CD4 T epitopes from hemagglutinin (HA), neuraminidase (NA), nuclear protein (NP), M1 matrix protein (MP), and PB1 of a seasonal H1N1 strain. We concluded that 15 of these 17 S-OIV peptides would induce responses of seasonal influenza virus-specific T cells. Of these, seven S-OIV sequences were identical to seasonal influenza virus sequences, while eight had at least one amino acid that was not conserved. T cells recognizing epitopes derived from these S-OIV antigens could be detected ex vivo. Most of these T cells expressed memory markers, although none of the donors had been exposed to S-OIV. Functional analysis revealed that specific amino acid differences in the sequences of these S-OIV peptides would not affect or partially affect memory T-cell responses. These findings suggest that without protective antibody responses, individuals vaccinated against seasonal influenza A may still benefit from preexisting cross-reactive memory CD4 T cells reducing their susceptibility to S-OIV infection.

scholarly journals STAT1 Is Essential for Antimicrobial Effector Function but Dispensable for Gamma Interferon Production during Toxoplasma gondii Infection

2004 ◽  
Vol 72 (3) ◽  
pp. 1257-1264 ◽  
Author(s):  
L. Cristina Gavrilescu ◽  
Barbara A. Butcher ◽  
Laura Del Rio ◽  
Gregory A. Taylor ◽  
Eric Y. Denkers
Keyword(s):  
T Cell ◽  
Toxoplasma Gondii ◽  
Intracellular Signaling ◽  
Acute Infection ◽  
Gamma Interferon ◽  
Interleukin 12 ◽  
Ifn Γ ◽  
Toxoplasma Gondii Infection ◽  
Oxide Synthase

ABSTRACT The opportunistic protozoan Toxoplasma gondii is a prototypic Th1-inducing pathogen inducing strong gamma interferon (IFN-γ) cytokine responses that are required to survive infection. Intracellular signaling intermediate STAT1 mediates many effects of IFN-γ and is implicated in activation of T-bet, a master regulator of Th1 differentiation. Here, we show that T. gondii-infected STAT1-null mice fail to upregulate the IFN-γ-dependent effector molecules inducible nitric oxide synthase (iNOS), IGTP, and LRG-47, which are required for mice to survive infection. Both T-bet and interleukin-12 receptor β2 (IL-12Rβ2) failed to undergo normal upregulation in response to T. gondii. Development of IFN-γ-producing CD4+ and CD8+ T lymphocytes was severely curtailed in the absence of STAT1, but a substantial level of STAT1-independent non-T-cell-derived IFN-γ was induced. Absence of STAT1 also resulted in increased IL-4, Arg1, Ym1, and Fizz1, markers of Th2 differentiation and alternative macrophage activation. Together, the results show that T. gondii induces STAT1-dependent T-lymphocyte and STAT1-independent non-T-cell IFN-γ production, but that effector functions of this type 1 cytokine cannot operate in the absence of STAT1, resulting in extreme susceptibility to acute infection.

scholarly journals Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Min Zhao ◽  
Kefang Liu ◽  
Jiejian Luo ◽  
Shuguang Tan ◽  
Chuansong Quan ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Seasonal Influenza ◽  
Vaccine Development ◽  
Cell Epitope ◽  
Cross Reactivity ◽  
Influenza Viruses ◽  
T Cell Epitope ◽  
Avian Influenza Viruses ◽  
Cell Responses

ABSTRACTAgainst a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.IMPORTANCEWe revealed preexisting but biased T-cell reactivity of pH1N1 influenza virus to human-infecting AIVs, which provided distinct protections. The cross-reactive T-cell recognition had a regular pattern that depended on the T-cell epitope matrix revealed via bioinformatics analysis. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.

scholarly journals Immunodominance in Virus-Induced CD8+ T-Cell Responses Is Dramatically Modified by DNA Immunization and Is Regulated by Gamma Interferon

2002 ◽  
Vol 76 (9) ◽  
pp. 4251-4259 ◽  
Author(s):  
Fernando Rodriguez ◽  
Stephanie Harkins ◽  
Mark K. Slifka ◽  
J. Lindsay Whitton
Keyword(s):  
T Cells ◽  
T Cell ◽  
Rational Design ◽  
Dna Vaccines ◽  
T Cell Responses ◽  
Gamma Interferon ◽  
Foreign Protein ◽  
Host Immune System ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT The phenomenon whereby the host immune system responds to only a few of the many possible epitopes in a foreign protein is termed immunodominance. Immunodominance occurs not only during microbial infection but also following vaccination, and clarification of the underlying mechanism may permit the rational design of vaccines which can circumvent immunodominance, thereby inducing responses to all epitopes, dominant and subdominant. Here, we show that immunodominance affects DNA vaccines and that the effects can be avoided by the simple expedient of epitope separation. DNA vaccines encoding isolated dominant and subdominant epitopes induce equivalent responses, confirming a previous demonstration that coexpression of dominant and subdominant epitopes on the same antigen-presenting cell (APC) is central to immunodominance. We conclude that multiepitope DNA vaccines should comprise a cocktail of plasmids, each with its own epitope, to allow maximal epitope dispersal among APCs. In addition, we demonstrate that subdominant responses are actively suppressed by dominant CD8+ T-cell responses and that gamma interferon (IFN-γ) is required for this suppression. Furthermore, priming of CD8+ T cells to a single dominant epitope results in strong suppression of responses to other normally dominant epitopes in immunocompetent mice, in effect rendering these epitopes subdominant; however, responses to these epitopes are increased 6- to 20-fold in mice lacking IFN-γ. We suggest that, in agreement with our previous observations, IFN-γ secretion by CD8+ T cells is highly localized, and we propose that its immunosuppressive effect is focused on the APC with which the dominant CD8+ T cell is in contact.

scholarly journals Performance of the QuantiFERON-Cytomegalovirus (CMV) Assay for Detection and Estimation of the Magnitude and Functionality of the CMV-Specific Gamma Interferon-Producing CD8+T-Cell Response in Allogeneic Stem Cell Transplant Recipients

2012 ◽  
Vol 19 (5) ◽  
pp. 791-796 ◽  
Author(s):  
María Ángeles Clari ◽  
Beatriz Muñoz-Cobo ◽  
Carlos Solano ◽  
Isabel Benet ◽  
Elisa Costa ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplant ◽  
T Cell Responses ◽  
Gamma Interferon ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Cell Responses ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACTThe performance of the QuantiFERON-cytomegalovirus (CMV) assay was compared to that of a flow cytometry intracellular cytokine staining (ICS) method for the detection of CMV-specific gamma interferon (IFN-γ)-producing CD8+T-cell responses in allogeneic stem cell transplant (allo-SCT) recipients and for estimations of their magnitude and functionality. A total of 90 whole-blood specimens from 23 allo-SCT recipients was analyzed by both methods. Overall, the percentage of specimens that yielded concordant results by both methods was 68.8% (κ = 0.691; 95% confidence interval [CI], 0.548 to 0.835), and the sensitivity of the QuantiFERON-CMV assay for the detection of positive IFN-γ T-cell responses (>0.2 IU/ml), taking the ICS method as the reference, was 76.3%. The magnitude of IFN-γ-producing CD8+T-cell responses to CMV-specific peptides measured with the QuantiFERON-CMV assay correlated significantly (σ = 0.695;P= <0.001) with that of the total IFN-γ-producing CD8+T cells and dual-functional (IFN-γ/tumor necrosis factor alpha [TNF-α] [σ = 0.652;P= <0.001] and IFN-γ/CD107a [σ = 0.690;P= <0.001]) and trifunctional (IFN-γ/TNF-α/CD107a [σ = 0.679;P= >0.001]) CMV-specific CD8+T-cell responses, as quantitated by ICS. In summary, the data indicated that the QuantiFERON-CMV assay is less sensitive than the ICS method for the detection of CMV-specific IFN-γ-producing CD8+T-cell responses in the allo-SCT setting. Nevertheless, it allowed the estimation of the total and polyfunctional CMV-specific IFN-γ-producing CD8+T-cell responses in specimens that tested positive by both methods.

scholarly journals CD4+ T-Cell- and Gamma Interferon-Dependent Protection against Murine Malaria by Immunization with Linear Synthetic Peptides from a Plasmodium yoelii17-Kilodalton Hepatocyte Erythrocyte Protein

1999 ◽  
Vol 67 (11) ◽  
pp. 5604-5614 ◽  
Author(s):  
Yupin Charoenvit ◽  
Victoria Fallarme Majam ◽  
Giampietro Corradin ◽  
John B. Sacci ◽  
Ruobing Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Synthetic Peptides ◽  
Vaccine Development ◽  
Surface Protein ◽  
T Cell Responses ◽  
Plasmodium Yoelii ◽  
Gamma Interferon ◽  
Cell Responses ◽  
Ifn Γ

ABSTRACT Most work on protective immunity against the pre-erythrocytic stages of malaria has focused on induction of antibodies that prevent sporozoite invasion of hepatocytes, and CD8+ T-cell responses that eliminate infected hepatocytes. We recently reported that immunization of A/J mice with an 18-amino-acid synthetic linear peptide from Plasmodium yoelii sporozoite surface protein 2 (SSP2) in TiterMax adjuvant induces sterile protection that is dependent on CD4+ T cells and gamma interferon (IFN-γ). We now report that immunization of inbred A/J mice and outbred CD1 mice with each of two linear synthetic peptides from the 17-kDa P. yoelii hepatocyte erythrocyte protein (HEP17) in the same adjuvant also induces protection against sporozoite challenge that is dependent on CD4+ T cells and IFN-γ. The SSP2 peptide and the two HEP17 peptides are recognized by B cells as well as T cells, and the protection induced by these peptides appears to be directed against the infected hepatocytes. In contrast to the peptide-induced protection, immunization of eight different strains of mice with radiation-attenuated sporozoites induces protection that is absolutely dependent on CD8+ T cells. Data represented here demonstrate that CD4+ T-cell-dependent protection can be induced by immunization with linear synthetic peptides. These studies therefore provide the foundation for an approach to pre-erythrocytic-stage malaria vaccine development, based on the induction of protective CD4+ T-cell responses, which will complement efforts to induce protective antibody and CD8+T-cell responses.

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