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  1. Article ; Online: Viral vaccines and CTL response.

    Woolard, Stacie N / Kumaraguru, Uday

    Journal of biomedicine & biotechnology

    2010  Volume 2010, Page(s) 141657

    Abstract: Immune induction by successful vaccine formulations seems to involve stimulation of both humoral and cellular arms of immunity. Nevertheless, CD8+ CTLs are of critical relevance in the context of intracellular infection and tumor for many reasons. The ... ...

    Abstract Immune induction by successful vaccine formulations seems to involve stimulation of both humoral and cellular arms of immunity. Nevertheless, CD8+ CTLs are of critical relevance in the context of intracellular infection and tumor for many reasons. The task of exerting antipathogen activity by CD8+ T cells, which principally function to control and eradicate intracellular pathogens, is enabled by constitutive expression of MHC class-I molecules on all tissue types. CTL induction offers hope for vaccines against pathogens that are resistant to neutralizing activity. This review discusses the mechanism of immune induction by some successful vaccines and based on the accrued evidence suggests ideas for improved design of CTL-inducing vaccines.
    MeSH term(s) Acute Disease ; Animals ; B-Lymphocytes/immunology ; Chronic Disease ; Humans ; Lymphocyte Activation/immunology ; T-Lymphocytes, Cytotoxic/immunology ; Viral Vaccines/immunology
    Chemical Substances Viral Vaccines
    Language English
    Publishing date 2010-03-31
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2052552-7
    ISSN 1110-7251 ; 1110-7243
    ISSN (online) 1110-7251
    ISSN 1110-7243
    DOI 10.1155/2010/141657
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Heterologous CD8 T cell immune response to HSV induced by toll like receptor ligands.

    Nandakumar, Subhadra / Kumaraguru, Uday

    Cellular immunology

    2010  Volume 261, Issue 2, Page(s) 114–121

    Abstract: A memory response is established following primary antigen exposure that stays more or less constant. It appears to adopt a set-point in magnitude but upon re-exposure the response is quicker and better and there is an upward shift in memory frequency ... ...

    Abstract A memory response is established following primary antigen exposure that stays more or less constant. It appears to adopt a set-point in magnitude but upon re-exposure the response is quicker and better and there is an upward shift in memory frequency that varies with individuals based on the exposure pattern to other microbes or its components. Our investigations were designed to test such differences of non-specific stimulation by PAMPs in lowering the threshold of activation. Neonatal mice were pre-exposed to TLR-ligands intermittently and later analyzed for its resilience to challenge with virus during adult-life. Secondly, adult mice with pre-existing memory to virus were exposed to various TLR-ligands and analyzed for their quality of memory response. The TLR-ligands exposed animals were better responders to a new agent exposure compared to the animals kept in sterile surroundings. Moreover, immune memory recall and the viral specific CD8(+) T cells response with TLR-ligands were comparable to the recall response with the cognate antigen. The results provide insights into the role of hyper-sanitized environment versus PAMPs mediated signaling in adaptive immunity and long-term immune memory.
    MeSH term(s) Adaptive Immunity/immunology ; Adult ; Animals ; Animals, Newborn ; CD8-Positive T-Lymphocytes/immunology ; Child ; Herpesvirus 1, Human/immunology ; Humans ; Immunologic Memory/immunology ; Ligands ; Mice ; Mice, Inbred C57BL ; Signal Transduction/immunology ; Spleen/cytology ; Survival Rate ; Toll-Like Receptors/immunology
    Chemical Substances Ligands ; Toll-Like Receptors
    Language English
    Publishing date 2010
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80094-6
    ISSN 1090-2163 ; 0008-8749
    ISSN (online) 1090-2163
    ISSN 0008-8749
    DOI 10.1016/j.cellimm.2009.11.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: T regulatory cells

    Kumaraguru Uday / Miller Christopher WT / Nandakumar Subhadra

    Clinical and Molecular Allergy, Vol 7, Iss 1, p

    an overview and intervention techniques to modulate allergy outcome

    2009  Volume 5

    Abstract: Abstract Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, ... ...

    Abstract Abstract Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is growing evidence in support of T cells with regulatory potential that operates in non-allergic individuals. These regulatory T cells occur naturally are called natural T regulatory cells (nTregs) and express the transcription factor Foxp3. They are selected in the thymus and move to the periphery. The CD4 Th cells in the periphery can be induced to become regulatory T cells and hence called induced or adaptive T regulatory cells. These cells can make IL-10 or TGF-b or both, by which they attain most of their suppressive activity. This review gives an overview of the regulatory T cells, their role in allergic diseases and explores possible interventionist approaches to manipulate Tregs for achieving therapeutic goals.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Allergy and Immunology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
    Subject code 610
    Language English
    Publishing date 2009-03-01T00:00:00Z
    Publisher BioMed Central
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: T regulatory cells: an overview and intervention techniques to modulate allergy outcome.

    Nandakumar, Subhadra / Miller, Christopher Wt / Kumaraguru, Uday

    Clinical and molecular allergy : CMA

    2009  Volume 7, Page(s) 5

    Abstract: Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is ... ...

    Abstract Dysregulated immune response results in inflammatory symptoms in the respiratory mucosa leading to asthma and allergy in susceptible individuals. The T helper type 2 (Th2) subsets are primarily involved in this disease process. Nevertheless, there is growing evidence in support of T cells with regulatory potential that operates in non-allergic individuals. These regulatory T cells occur naturally are called natural T regulatory cells (nTregs) and express the transcription factor Foxp3. They are selected in the thymus and move to the periphery. The CD4 Th cells in the periphery can be induced to become regulatory T cells and hence called induced or adaptive T regulatory cells. These cells can make IL-10 or TGF-b or both, by which they attain most of their suppressive activity. This review gives an overview of the regulatory T cells, their role in allergic diseases and explores possible interventionist approaches to manipulate Tregs for achieving therapeutic goals.
    Language English
    Publishing date 2009-03-12
    Publishing country England
    Document type Journal Article
    ZDB-ID 2126317-6
    ISSN 1476-7961 ; 1476-7961
    ISSN (online) 1476-7961
    ISSN 1476-7961
    DOI 10.1186/1476-7961-7-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: IL-21 and IL-15 cytokine DNA augments HSV specific effector and memory CD8+ T cell response.

    Rodrigues, Luiz / Nandakumar, Subhadra / Bonorino, Cristina / Rouse, Barry T / Kumaraguru, Uday

    Molecular immunology

    2009  Volume 46, Issue 7, Page(s) 1494–1504

    Abstract: The recurrence of lesions and transmission of Herpes simplex virus is dependent on the number and function of viral specific CD8(+) T cells, especially the memory T cells. The generation, turnover and set point of this cell population is maintained by ... ...

    Abstract The recurrence of lesions and transmission of Herpes simplex virus is dependent on the number and function of viral specific CD8(+) T cells, especially the memory T cells. The generation, turnover and set point of this cell population is maintained by different factors like exposure to antigen, cytokines and co-stimulatory molecules. However, the contribution of these factors in the generation and maintenance of the memory CD8(+) T cell population is still controversial, since it is not clear if homeostatic proliferation driven by cytokines can overcome T cell receptor (TCR) signaling. Since, interleukin 15 (IL-15) and interleukin 21 (IL-21) are cytokines implicated in homeostatic control of CD8(+) T cell pool, we constructed and used expression plasmids coding for IL-15 (pIL-15) and IL-21 (pIL-21) to expand HSV specific CD8(+) T cells in an animal model. Our results showed that the IL-21 increased the frequency of CD8(+) T cells in the absence of antigen, although the magnitude of this response was dependent on TCR signaling. Both pIL-15 and pIL-21 boosted the numbers of antigen specific CD8(+) IFNgamma producing cells in the primary response. In the memory phase, numbers of CD8(+) CD44(high) as well as CD8(+) T cells producing IFN-gamma and TNF-alpha were increased when pIL-15 and pIL-21 were used alone or in combination, compared to vector treatment only, and association of antigen further increased the proliferative response. Our data suggest that genetic treatment with pIL-15 and pIL-21 in the presence or absence of cognate antigen can contribute to immune-enhancement against HSV.
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/immunology ; Cells, Cultured ; Cercopithecus aethiops ; DNA/immunology ; DNA/physiology ; Female ; Genetic Therapy ; Humans ; Immunologic Memory/physiology ; Immunotherapy/methods ; Interleukin-15/genetics ; Interleukin-15/immunology ; Interleukins/genetics ; Interleukins/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Rats ; Simplexvirus/immunology ; T-Cell Antigen Receptor Specificity ; T-Lymphocytes/immunology ; Vero Cells
    Chemical Substances Interleukin-15 ; Interleukins ; interleukin-21 ; DNA (9007-49-2)
    Language English
    Publishing date 2009-04
    Publishing country England
    Document type Evaluation Studies ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 424427-8
    ISSN 1872-9142 ; 0161-5890
    ISSN (online) 1872-9142
    ISSN 0161-5890
    DOI 10.1016/j.molimm.2008.12.033
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Natural killer cells as novel helpers in anti-herpes simplex virus immune response.

    Nandakumar, Subhadra / Woolard, Stacie N / Yuan, Dorothy / Rouse, Barry T / Kumaraguru, Uday

    Journal of virology

    2008  Volume 82, Issue 21, Page(s) 10820–10831

    Abstract: Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be ... ...

    Abstract Innate defenses help to eliminate infection, but some of them also play a major role in shaping the magnitude and efficacy of the adaptive immune response. With regard to influencing subsequent adaptive immunity, NK cells aided by dendritic cells may be the most relevant components of the innate reaction to herpes simplex virus (HSV) infection. We confirm that mice lacking or depleted of NK cells are susceptible to HSV-induced lesions. The quantity and quality of CD8(+) cytotoxic T lymphocytes generated in the absence of NK cells were diminished, thereby contributing to susceptibility to HSV-induced encephalitis. We demonstrate a novel helper role for NK cells, in that NK cells compensate for the loss of CD4 helper T cells and NK cell supplementation enhances the function of wild type anti-HSV CD8 T cells. In addition, NK cells were able to partially rescue the dysfunctional CD8(+) T cells generated in the absence of CD4 T helper cells, thereby performing a novel rescue function. Hence, NK cells may well be exploited for enhancing and rescuing the T-cell response in situations where the CD4 helper response is affected.
    MeSH term(s) Animals ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Chlorocebus aethiops ; Encephalitis, Viral/immunology ; Herpesvirus 1, Human/immunology ; Killer Cells, Natural/immunology ; Leukocyte Reduction Procedures ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; T-Lymphocytes, Helper-Inducer/immunology
    Language English
    Publishing date 2008-08-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.00365-08
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions.

    Suvas, Susmit / Azkur, Ahmet Kursat / Kim, Bum Seok / Kumaraguru, Uday / Rouse, Barry T

    Journal of immunology (Baltimore, Md. : 1950)

    2004  Volume 172, Issue 7, Page(s) 4123–4132

    Abstract: CD4(+)CD25(+) regulatory T cells (T(reg)) can inhibit a variety of autoimmune and inflammatory diseases, but their involvement in regulating virus-induced immunopathology is not known. We have evaluated the role of T(reg) in viral immunopathological ... ...

    Abstract CD4(+)CD25(+) regulatory T cells (T(reg)) can inhibit a variety of autoimmune and inflammatory diseases, but their involvement in regulating virus-induced immunopathology is not known. We have evaluated the role of T(reg) in viral immunopathological lesion stromal keratitis. This frequent cause of human blindness results from a T cell-mediated immunoinflammatory response to HSV in the corneal stroma. The results show that lesions were significantly more severe if mice were depleted of T(reg) before infection. The T(reg) was also shown to modulate lesion expression induced by adoptive transfer of pathogenic CD4(+) T cells in infected SCID recipients. The mechanism of T(reg) control of stromal keratitis involved suppressed antiviral immunity and impaired expression of the molecule required for T cell migration to lesion sites. Interestingly, T(reg) isolated from ocular lesions in nondepleted mice showed in vitro inhibitory effects involving IL-10, but were not very effective in established lesions. Our results decipher the in vivo role of T(reg) in a virus-induced immunopathology and imply that manipulation of regulatory cell function represents a useful approach to control viral-induced immunoinflammatory disease.
    MeSH term(s) Adoptive Transfer ; Animals ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/pathology ; CD4-Positive T-Lymphocytes/transplantation ; Cell Movement/immunology ; Cells, Cultured ; Female ; Herpesvirus 1, Human/immunology ; Immunophenotyping ; Immunosuppression ; Keratitis, Herpetic/immunology ; Keratitis, Herpetic/pathology ; Keratitis, Herpetic/prevention & control ; Lymphocyte Depletion ; Lymphopenia/immunology ; Lymphopenia/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; Receptors, Interleukin-2/administration & dosage ; Receptors, Interleukin-2/biosynthesis ; Severity of Illness Index ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocyte Subsets/pathology ; T-Lymphocyte Subsets/transplantation
    Chemical Substances Receptors, Interleukin-2
    Language English
    Publishing date 2004-04-26
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.172.7.4123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses.

    Suvas, Susmit / Kumaraguru, Uday / Pack, Christopher D / Lee, Sujin / Rouse, Barry T

    The Journal of experimental medicine

    2003  Volume 198, Issue 6, Page(s) 889–901

    Abstract: Naturally occurring CD4+CD25+ regulatory T cells appear important to prevent activation of autoreactive T cells. This article demonstrates that the magnitude of a CD8+ T cell-mediated immune response to an acute viral infection is also subject to control ...

    Abstract Naturally occurring CD4+CD25+ regulatory T cells appear important to prevent activation of autoreactive T cells. This article demonstrates that the magnitude of a CD8+ T cell-mediated immune response to an acute viral infection is also subject to control by CD4+CD25+ T regulatory cells (Treg). Accordingly, if natural Treg were depleted with specific anti-CD25 antibody before infection with HSV, the resultant CD8+ T cell response to the immunodominant peptide SSIEFARL was significantly enhanced. This was shown by several in vitro measures of CD8+ T cell reactivity and by assays that directly determine CD8+ T cell function, such as proliferation and cytotoxicity in vivo. The enhanced responsiveness in CD25-depleted animals was between three- and fourfold with the effect evident both in the acute and memory phases of the immune response. Surprisingly, HSV infection resulted in enhanced Treg function with such cells able to suppress CD8+ T cell responses to both viral and unrelated antigens. Our results are discussed both in term of how viral infection might temporarily diminish immunity to other infectious agents and their application to vaccines. Thus, controlling suppressor effects at the time of vaccination could result in more effective immunity.
    MeSH term(s) Adoptive Transfer ; Animals ; Biomarkers ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Female ; Herpes Simplex/immunology ; Herpes Simplex/metabolism ; Herpesvirus 1, Human/immunology ; Herpesvirus 1, Human/metabolism ; Immunologic Memory/physiology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Receptors, Interleukin-2/immunology ; Receptors, Interleukin-2/metabolism ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism
    Chemical Substances Biomarkers ; Receptors, Interleukin-2
    Language English
    Publishing date 2003-09-15
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20030171
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Cross-talk between programmed death-1 and suppressor of cytokine signaling-1 in inhibition of IL-12 production by monocytes/macrophages in hepatitis C virus infection.

    Zhang, Ying / Ma, Cheng J / Ni, Lei / Zhang, Chun L / Wu, Xiao Y / Kumaraguru, Uday / Li, Chuan F / Moorman, Jonathan P / Yao, Zhi Q

    Journal of immunology (Baltimore, Md. : 1950)

    2011  Volume 186, Issue 5, Page(s) 3093–3103

    Abstract: Hepatitis C virus (HCV) dysregulates innate immune responses and induces persistent viral infection. We previously demonstrated that HCV core protein impairs IL-12 expression by monocytes/macrophages (M/M(Φ)s) through interaction with a complement ... ...

    Abstract Hepatitis C virus (HCV) dysregulates innate immune responses and induces persistent viral infection. We previously demonstrated that HCV core protein impairs IL-12 expression by monocytes/macrophages (M/M(Φ)s) through interaction with a complement receptor gC1qR. Because HCV core-mediated lymphocyte dysregulation occurs through the negative immunomodulators programmed death-1 (PD-1) and suppressor of cytokine signaling-1 (SOCS-1), the aim of this study was to examine their role in HCV core-mediated IL-12 suppression in M/M(Φ)s. We analyzed TLR-stimulated, primary CD14(+) M/M(Φ)s from chronically HCV-infected and healthy subjects or the THP-1 cell line for PD-1, SOCS-1, and IL-12 expression following HCV core treatment. M/M(Φ)s from HCV-infected subjects at baseline exhibited comparatively increased PD-1 expression that significantly correlated with the degree of IL-12 inhibition. M/M(Φ)s isolated from healthy and HCV-infected individuals and treated with HCV core protein displayed increased PD-1 and SOCS-1 expression and decreased IL-12 expression, an effect that was also observed in cells treated with gC1qR's ligand, C1q. Blocking gC1qR rescued HCV core-induced PD-1 upregulation and IL-12 suppression, whereas blocking PD-1 signaling enhanced IL-12 production and decreased the expression of SOCS-1 induced by HCV core. Conversely, silencing SOCS-1 expression using small interfering RNAs increased IL-12 expression and inhibited PD-1 upregulation. PD-1 and SOCS-1 were found to associate by coimmunoprecipitation studies, and blocking PD-1 or silencing SOCS-1 in M/M(Φ) led to activation of STAT-1 during TLR-stimulated IL-12 production. These data suggested that HCV core/gC1qR engagement on M/M(Φ)s triggers the expression of PD-1 and SOCS-1, which can associate to deliver negative signaling to TLR-mediated pathways controlling expression of IL-12, a key cytokine linking innate and adaptive immunity.
    MeSH term(s) Adult ; Aged ; Antigens, CD/physiology ; Apoptosis Regulatory Proteins/physiology ; Cell Communication/immunology ; Cell Line, Tumor ; Down-Regulation/immunology ; Female ; Hepatitis C, Chronic/immunology ; Hepatitis C, Chronic/metabolism ; Hepatitis C, Chronic/pathology ; Humans ; Interleukin-12/antagonists & inhibitors ; Interleukin-12/biosynthesis ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/pathology ; Male ; Membrane Glycoproteins/metabolism ; Middle Aged ; Monocytes/immunology ; Monocytes/metabolism ; Monocytes/pathology ; Programmed Cell Death 1 Receptor ; Receptors, Complement/metabolism ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling Proteins/physiology ; Toll-Like Receptors/physiology
    Chemical Substances Antigens, CD ; Apoptosis Regulatory Proteins ; Membrane Glycoproteins ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Receptors, Complement ; SOCS1 protein, human ; Suppressor of Cytokine Signaling 1 Protein ; Suppressor of Cytokine Signaling Proteins ; Toll-Like Receptors ; complement 1q receptor ; Interleukin-12 (187348-17-0)
    Language English
    Publishing date 2011-03-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.1002006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Induction of CD8 T-cell-specific systemic and mucosal immunity against herpes simplex virus with CpG-peptide complexes.

    Gierynska, Malgorzata / Kumaraguru, Uday / Eo, Seong-Kug / Lee, Sujin / Krieg, Arthur / Rouse, Barry T

    Journal of virology

    2001  Volume 76, Issue 13, Page(s) 6568–6576

    Abstract: Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs exert powerful adjuvant activity in vivo and in vitro. Administered with antigen they induce a population of antigen-specific CD8+ T cells. In this study we immunized C57BL/6 mice with ... ...

    Abstract Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs exert powerful adjuvant activity in vivo and in vitro. Administered with antigen they induce a population of antigen-specific CD8+ T cells. In this study we immunized C57BL/6 mice with bioactive CpG ODN combined with an immunodominant epitope derived from herpes simplex virus (HSV) glycoprotein B (amino acids 498 to 505; SSIEFARL) and analyzed the magnitude and durability of the peptide-specific response. The effectiveness of the CD8+ T-cell response as measured by peptide-specific tetramers, peptide-induced intracellular gamma interferon expression, and resistance to systemic and mucosal challenge during the acute and memory phases was compared with the response induced by immunization with recombinant vaccinia virus encoding SSIEFARL as a minigene (VvgB(498-505)). Confirming the reports of others, our results demonstrate that the CpG ODN-peptide approach generates an antigen-specific CD8+ T-cell population, but the frequency of CD8+ T cells is lower than that induced by VvgB(498-505). Nevertheless, the protection level was comparable when mice were systemically and mucosally challenged during the acute phase. However, such responses by both groups waned with time and were functionally less effective. Still, our results indicate that the CpG ODN-peptide immunization system holds promise as a means of selectively inducing a CD8+ T-cell response against HSV.
    MeSH term(s) Animals ; CD8-Positive T-Lymphocytes/immunology ; Dinucleoside Phosphates/chemistry ; Dinucleoside Phosphates/immunology ; Female ; Herpes Simplex/immunology ; Herpes Simplex/prevention & control ; Herpesvirus 1, Human/immunology ; Herpesvirus 1, Human/pathogenicity ; Herpesvirus Vaccines/immunology ; Immunity, Mucosal ; Immunodominant Epitopes/chemistry ; Immunologic Memory ; Mice ; Mice, Inbred C57BL ; Peptides/chemistry ; Peptides/immunology ; Vaccination ; Vagina/immunology ; Vagina/virology ; Viral Envelope Proteins/chemistry ; Viral Envelope Proteins/immunology
    Chemical Substances Dinucleoside Phosphates ; Herpesvirus Vaccines ; Immunodominant Epitopes ; Peptides ; Viral Envelope Proteins ; glycoprotein B, Simplexvirus ; cytidylyl-3'-5'-guanosine (2382-65-2)
    Language English
    Publishing date 2001-05-07
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.76.13.6568-6576.2002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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