Incomplete effector/memory differentiation of antigen-primed CD8+ T cells in gene gun DNA-vaccinated mice.

Abstract:

:DNA vaccination is an efficient way to induce CD8+ T cell memory, but it is still unclear to what extent such memory responses afford protection in vivo. To study this, we induced CD8+ memory responses directed towards defined viral epitopes, using DNA vaccines encoding immunodominant MHC class I-restricted epitopes of lymphocytic choriomeningitis virus covalently linked to beta2-microglobulin. This vaccine construct primed for a stronger recall response than did a more conventional minigene construct. Despite this, vaccinated mice were only protected against systemic infection whereas protection against the consequences of peripheral challenge was limited. Phenotypic analysis revealed that DNA vaccine-primed CD8+ T cells in uninfected mice differed from virus-primed CD8+ T cells particularly regarding expression of very-late antigen (VLA)-4, an adhesion molecule important for targeting T cells to inflammatory sites. Thus, our DNA vaccine induces a long-lived memory CD8+ T cell population that provides efficient protection against high-dose systemic infection. However, viral replication in solid non-lymphoid organs is not curtailed sufficiently fast to prevent significant virus-induced inflammation. Our results suggest that this is due to qualitative limitations of the primed CD8+ T cells.

journal_name

Eur J Immunol

authors

Bartholdy C,Stryhn A,Hansen NJ,Buus S,Thomsen AR

doi

10.1002/eji.200323928

keywords:

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

1941-8

issue

7

eissn

0014-2980

issn

1521-4141

journal_volume

33

pub_type

杂志文章
  • The effect of anchor residue modifications on the stability of major histocompatibility complex class I-peptide interactions.

    abstract::Anchor residues in peptides determine the specificity of binding to major histocompatibility complex class I molecules through interactions of their side chains with pockets in the peptide-binding groove. We have compared the kinetics of association of a Sendai virus nucleoprotein-derived peptide (FAPGNYPAL, termed SV...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830230411

    authors: Neefjes JJ,Dierx J,Ploegh HL

    更新日期:1993-04-01 00:00:00

  • Mycobacterium chelonae sensitisation induces CD4(+)-mediated cytotoxicity against BCG.

    abstract::Significant variability in efficacy of live Mycobacterium bovis BCG as a tuberculosis vaccine is observed globally. Effects of pre-vaccination sensitisation to non-tuberculous environmental mycobacteria (Env) are suspected to underlie this phenomenon, but the mechanisms remain unclear. We postulated that it could be d...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200838933

    authors: Ho P,Zhang L,Wei X,Seah GT

    更新日期:2009-07-01 00:00:00

  • Interleukin 2 stimulates serine phosphorylation of CD45 in CTLL-2.4 cells.

    abstract::Ligation of interleukin 2 (IL2) is known to regulate both protein tyrosine and serine/threonine phosphorylation. A family of leukocyte transmembrane proteins whose cytoplasmic domain exhibits intrinsic protein tyrosine phosphatase activity is collectively called CD45 and is identified by a set of common cell surface e...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830210438

    authors: Valentine MA,Widmer MB,Ledbetter JA,Pinault F,Voice R,Clark EA,Gallis B,Brautigan DL

    更新日期:1991-04-01 00:00:00

  • IL-18 enhances IFN-gamma-induced production of CXCL9, CXCL10, and CXCL11 in human keratinocytes.

    abstract::IL-18 is involved in the pathogenesis of atopic dermatitis, psoriasis, and allergic contact dermatitis. CXCL9, CXCL10, and CXCL11 recruit type 1 T cells, and the production of these chemokines by keratinocytes is enhanced in these dermatoses. We examined the in vitro effects of IL-18 on IFN-gamma-induced CXCL9, CXCL10...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200636420

    authors: Kanda N,Shimizu T,Tada Y,Watanabe S

    更新日期:2007-02-01 00:00:00

  • Establishment of mouse thymic nurse cell clones from a spontaneous BALB/c thymic tumor.

    abstract::This is the first report on the establishment of the readily identifiable and functioning thymic nurse cell (TNC) clones from the mouse thymus. In the course of the culture of an epithelial cell line using a medium with a low concentration of Ca2+ from the spontaneous BALB/c thymic tumor, lymphocytes as well as thymic...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830180525

    authors: Itoh T,Doi H,Chin S,Nishimura T,Kasahara S

    更新日期:1988-05-01 00:00:00

  • Effect of cloned interferon-gamma on expression of H-2 and Ia antigens on cell lines of hemopoietic, lymphoid, epithelial, fibroblastic and neuronal origin.

    abstract::Interferon-gamma (IFN-gamma), tested in the form of the product of a cloned murine IFN-gamma gene, was found to increase the expression of H-2 antigens on cultured cell lines of a wide variety of cell types including factor-dependent hemopoietic cells, pre-B and B cells, macrophages, T cells, mast cells and cell lines...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830140110

    authors: Wong GH,Clark-Lewis I,Harris AW,Schrader JW

    更新日期:1984-01-01 00:00:00

  • The effect of pregnancy on the uterine NK cell KIR repertoire.

    abstract::The major leukocyte population in the decidua during the first trimester of pregnancy consists of NK cells that express receptors capable of recognizing MHC class I molecules expressed by placental trophoblast. These include members of the killer immunoglobulin-like receptor (KIR) family, the two-domain KIR (KIR2D), w...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201141445

    authors: Male V,Sharkey A,Masters L,Kennedy PR,Farrell LE,Moffett A

    更新日期:2011-10-01 00:00:00

  • The human OX40 homolog: cDNA structure, expression and chromosomal assignment of the ACT35 antigen.

    abstract::Tissue distribution and expression on mitogen and virally stimulated lymphocytes render the ACT35 molecule a human lymphocyte activation antigen which as yet could not be clustered. Expression cloning of the ACT35 antigen from a pCDM8 library of the HUT-102 cell line revealed strong homology of the cDNA and its encode...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830240329

    authors: Latza U,Dürkop H,Schnittger S,Ringeling J,Eitelbach F,Hummel M,Fonatsch C,Stein H

    更新日期:1994-03-01 00:00:00

  • DMBT1 functions as pattern-recognition molecule for poly-sulfated and poly-phosphorylated ligands.

    abstract::Deleted in malignant brain tumors 1 (DMBT1) is a secreted glycoprotein displaying a broad bacterial-binding spectrum. Recent functional and genetic studies linked DMBT1 to the suppression of LPS-induced TLR4-mediated NF-kappaB activation and to the pathogenesis of Crohn's disease. Here, we aimed at unraveling the mole...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200838689

    authors: End C,Bikker F,Renner M,Bergmann G,Lyer S,Blaich S,Hudler M,Helmke B,Gassler N,Autschbach F,Ligtenberg AJ,Benner A,Holmskov U,Schirmacher P,Nieuw Amerongen AV,Rosenstiel P,Sina C,Franke A,Hafner M,Kioschis P,Schre

    更新日期:2009-03-01 00:00:00

  • Selective induction of interleukin-1 receptor antagonist and interleukin-8 in human monocytes by normal polyspecific IgG (intravenous immunoglobulin).

    abstract::We have investigated the effects of intravenous immunoglobulin (IVIg), a therapeutic preparation of normal human polyspecific IgG, on the synthesis and release of cytokines by peripheral blood monocytes. IVIg was found to selectively induce gene transcription and secretion of interleukin-1 receptor antagonist (IL-1ra)...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250521

    authors: Ruiz de Souza V,Carreno MP,Kaveri SV,Ledur A,Sadeghi H,Cavaillon JM,Kazatchkine MD,Haeffner-Cavaillon N

    更新日期:1995-05-01 00:00:00

  • Tumor-specific CD4+ T cells maintain effector and memory tumor-specific CD8+ T cells.

    abstract::Immunotherapies that augment antitumor T cells have had recent success for treating patients with cancer. Here we examined whether tumor-specific CD4(+) T cells enhance CD8(+) T-cell adoptive immunotherapy in a lymphopenic environment. Our model employed physiological doses of tyrosinase-related protein 1-specific CD4...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201343718

    authors: Church SE,Jensen SM,Antony PA,Restifo NP,Fox BA

    更新日期:2014-01-01 00:00:00

  • Different affinity windows for virus and cancer-specific T-cell receptors: implications for therapeutic strategies.

    abstract::T-cell destiny during thymic selection depends on the affinity of the TCR for autologous peptide ligands presented in the context of MHC molecules. This is a delicately balanced process; robust binding leads to negative selection, yet some affinity for the antigen complex is required for positive selection. All TCRs o...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201242606

    authors: Aleksic M,Liddy N,Molloy PE,Pumphrey N,Vuidepot A,Chang KM,Jakobsen BK

    更新日期:2012-12-01 00:00:00

  • Anti-Thy-1-induced proliferation of immature thymocytes expressing the CD3-associated gamma/delta heterodimer.

    abstract::A series of rat monoclonal antibodies (mAb) directed against the Thy-1 molecule have been evaluated for their ability to stimulate immature (CD4-8-) murine thymocytes. CD4-8- thymocytes could be induced to proliferate by several anti-Thy-1 mAb provided that exogenous interleukin 1 or interleukin 2 was provided. Appare...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830171127

    authors: MacDonald HR,Miescher GC,Howe RC

    更新日期:1987-11-01 00:00:00

  • CD5 blockade enhances ex vivo CD8+ T cell activation and tumour cell cytotoxicity.

    abstract::CD5 is expressed on T cells and a subset of B cells (B1a). It can attenuate TCR signalling and impair CTL activation and is a therapeutic targetable tumour antigen expressed on leukemic T and B cells. However, the potential therapeutic effect of functionally blocking CD5 to increase T cell anti-tumour activity against...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201948309

    authors: Alotaibi F,Rytelewski M,Figueredo R,Zareardalan R,Zhang M,Ferguson PJ,Maleki Vareki S,Najajreh Y,El-Hajjar M,Zheng X,Min WP,Koropatnick J

    更新日期:2020-05-01 00:00:00

  • TCR signalling network organization at the immunological synapses of murine regulatory T cells.

    abstract::Regulatory T (Treg) cells require T-cell receptor (TCR) signalling to exert their immunosuppressive activity, but the precise organization of the TCR signalling network compared to conventional T (Tconv) cells remains elusive. By using accurate mass spectrometry and multi-epitope ligand cartography (MELC) we character...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.201747041

    authors: van Ham M,Teich R,Philipsen L,Niemz J,Amsberg N,Wissing J,Nimtz M,Gröbe L,Kliche S,Thiel N,Klawonn F,Hubo M,Jonuleit H,Reichardt P,Müller AJ,Huehn J,Jänsch L

    更新日期:2017-12-01 00:00:00

  • Direct visualization of the dynamics of antigen presentation in human cells infected with cytomegalovirus revealed by antibodies mimicking TCR specificity.

    abstract::There are no direct means to study class I MHC presentation in human normal or diseased cells. Using CMV-infected human cells and applying novel mAb that mimic T-cell receptor specificity directed toward the immunogenic epitope of the viral pp65 protein presented on HLA-A2 molecules, we directly imaged the dynamics of...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200939875

    authors: Makler O,Oved K,Netzer N,Wolf D,Reiter Y

    更新日期:2010-06-01 00:00:00

  • The "natural resistance" to bone marrow allografts in normal and athymic nude rats. Rapid cytotoxic reactions both in vivo and in vitro.

    abstract::To elucidate the rapid destruction of allogeneic bone marrow (BM) grafts in nonsensitized rats we have assessed: (a) the 21-h tissue localization of 51Cr-labeled allogeneic vs. syngeneic BM cells, (b) the ability of allogeneic BM cells to proliferate in the BM or irradiated recipients, (c) the survival of allogeneic v...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830140906

    authors: Rolstad B,Benestad HB

    更新日期:1984-09-01 00:00:00

  • Anti-B cell autoantibodies encoded by VH 4-21 genes in human fetal spleen do not require in vivo somatic selection.

    abstract::We isolated immunoglobulin (Ig) VH4 genes that were rearranged in the genomic DNA of 160 day human fetal spleen. Productively rearranged VH 4-21 genes were cloned into pRTM1, a human IgM expression vector. This allowed us to generate IgM kappa-expressing transfectomas by co-transfecting each of these constructs with p...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830241204

    authors: Parr TB,Johnson TA,Silberstein LE,Kipps TJ

    更新日期:1994-12-01 00:00:00

  • A novel human HER2-derived peptide homologous to the mouse K(d)-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals.

    abstract::A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K(d)-restricted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor rejection antigen in an in vivo assay. Since the anchor motif of mouse K(d) for peptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200011)30:11<3338::AID-IMMU3338>

    authors: Okugawa T,Ikuta Y,Takahashi Y,Obata H,Tanida K,Watanabe M,Imai S,Furugen R,Nagata Y,Toyoda N,Shiku H

    更新日期:2000-11-01 00:00:00

  • Identification and expression of two forms of the human transforming growth factor-beta-binding protein endoglin with distinct cytoplasmic regions.

    abstract::Endoglin is an homodimeric membrane antigen with capacity to bind transforming growth factor-beta (TGF-beta) and whose expression is up-regulated on myeloid cells upon differentiation to macrophages. We have isolated full-length cDNA clones from a lambda gt 10 library, prepared from phorbol 12-myristate 13-acetate-dif...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830230943

    authors: Bellón T,Corbí A,Lastres P,Calés C,Cebrián M,Vera S,Cheifetz S,Massague J,Letarte M,Bernabéu C

    更新日期:1993-09-01 00:00:00

  • Categorical selection of the antibody repertoire in splenic B cells.

    abstract::In the bone marrow, the passage of developing B cells through critical checkpoints of differentiation is associated with a reduction of specific categories of CDR3 of the Ig heavy chain (CDR-H3), particularly those with excessive hydrophobic or charged amino acids and those with a length of eight or fewer residues. To...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200636569

    authors: Schelonka RL,Tanner J,Zhuang Y,Gartland GL,Zemlin M,Schroeder HW Jr

    更新日期:2007-04-01 00:00:00

  • Modulation of murine dendritic cell function by adenine nucleotides and adenosine: involvement of the A(2B) receptor.

    abstract::Adenosine triphosphate has previously been shown to induce semi-mature human monocyte-derived dendritic cells (DC). These are characterized by the up-regulation of co-stimulatory molecules, the inhibition of IL-12 and the up-regulation of some genes involved in immune tolerance, such as thrombospondin-1 and indoleamin...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200737781

    authors: Ben Addi A,Lefort A,Hua X,Libert F,Communi D,Ledent C,Macours P,Tilley SL,Boeynaems JM,Robaye B

    更新日期:2008-06-01 00:00:00

  • Cell division in the compartment of naive and memory T lymphocytes.

    abstract::Expression of activation markers and proliferative status were measured in peripheral CD4+ and CD8+ T cells of various T cell receptor (TCR)-transgenic mice either before or after intentional antigenic stimulation. In the absence of intentional immunization, CD4+ T cells persisted as resting or partially activated and...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830261251

    authors: Bruno L,von Boehmer H,Kirberg J

    更新日期:1996-12-01 00:00:00

  • IL-10 enhances NK cell proliferation, cytotoxicity and production of IFN-gamma when combined with IL-18.

    abstract::Previous studies have shown that IL-10 inhibits the accessory cell functions required for production of IFN-gamma by T cells and NK cells. Our results show that although IL-10 did not induce the production of IFN-gamma by NK cells, it did enhance the ability of IL-18 to stimulate NK cell production of IFN-gamma. In ad...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/(SICI)1521-4141(199909)29:09<2658::AID-IMM

    authors: Cai G,Kastelein RA,Hunter CA

    更新日期:1999-09-01 00:00:00

  • Sequential development of helper and suppressor functions, antibody titers and functional avidities to a streptococcal antigen in rhesus monkeys.

    abstract::Sequential development of antibody titer, functional avidity, helper and suppressor activities were investigated in rhesus monkeys. These were immunized with a single dose of 0.1 microgram to 10 mg of a streptococcal protein antigen (SA) in aluminium hydroxide. The IgG antibody titers followed the classical pattern fi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830140909

    authors: Lehner T,Caldwell J,Avery J

    更新日期:1984-09-01 00:00:00

  • Altered expression of miR-17-5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients.

    abstract::MicroRNA (miRNA) are a class of post-transcriptional regulators of gene expression targeting mRNA for translational repression and/or degradation. We analyzed the expression of 365 miRNA in lymphocytes in relapsing-remitting MS patients, and show the first evidence for distinct miRNA expression profiles in CD4(+), CD8...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200940032

    authors: Lindberg RL,Hoffmann F,Mehling M,Kuhle J,Kappos L

    更新日期:2010-03-01 00:00:00

  • The immunodominant epitope of lipocalin allergen Bos d 2 is suboptimal for human T cells.

    abstract::We have proposed earlier that the poor capacity of the lipocalin allergen Bos d 2 to stimulate highly allergic subjects' peripheral blood mononuclear cells could be ascribed to endogenous lipocalins and could be related to the allergenic potential of the molecule. Here, we have characterized the proliferative and cyto...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.200322952

    authors: Kinnunen T,Buhot C,Närvänen A,Rytkönen-Nissinen M,Saarelainen S,Pouvelle-Moratille S,Rautiainen J,Taivainen A,Maillère B,Mäntyjärvi R,Virtanen T

    更新日期:2003-06-01 00:00:00

  • Granzyme B and perforin can be used as predictive markers of acute rejection in heart transplantation.

    abstract::We have investigated perforin and granzyme B expression in graft-infiltrating lymphocytes of patients who underwent heart transplantation. Those proteins are commonly present in the cytoplasmic granules of cytotoxic T lymphocytes and are released upon effector-target cell interaction. From 28 patients 103 endomyocardi...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830240136

    authors: Legros-Maïda S,Soulié A,Benvenuti C,Wargnier A,Vallée N,Berthou C,Guillet J,Sasportes M,Sigaux N

    更新日期:1994-01-01 00:00:00

  • Human T cell leukemia virus type I Tax enhances IL-4 gene expression in T cells.

    abstract::The human T cell leukemia virus type-1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL). Since the HTLV-I-encoded transactivator Tax has been shown to activate many cellular genes including cytokine genes interleukin (IL-)1alpha, 2, 5, 6, 8, 10 and 15, we ask whether Tax also affects IL-4 expression. In ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/1521-4141(200109)31:9<2623::aid-immu2623>3

    authors: Li-Weber M,Giaisi M,Chlichlia K,Khazaie K,Krammer PH

    更新日期:2001-09-01 00:00:00

  • Evidence for Th2 cell-mediated suppression of antibody responses in transgenic, beef insulin-tolerant mice.

    abstract::Clonal deletion, anergy and suppression have all been considered mechanisms of immunological tolerance. Although adoptive transfer of immunosuppression has been shown to occur in the periphery, particularly for transplantation tolerance, it has proven difficult to characterize this phenomenon further, due to the lack ...

    journal_title:European journal of immunology

    pub_type: 杂志文章

    doi:10.1002/eji.1830250917

    authors: Teng YT,Gorczynski RM,Iwasaki S,Williams DB,Hozumi N

    更新日期:1995-09-01 00:00:00