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  1. Article: Type I Interferon-Independent Dendritic Cell Priming and Antitumor T Cell Activation Induced by a

    Takeda, Yohei / Azuma, Masahiro / Funami, Kenji / Shime, Hiroaki / Matsumoto, Misako / Seya, Tsukasa

    Frontiers in immunology

    2018  Volume 9, Page(s) 496

    Abstract: Mycoplasma ... ...

    Abstract Mycoplasma fermentans
    MeSH term(s) Animals ; Bacterial Proteins/chemistry ; Bacterial Proteins/pharmacology ; Cell Line, Tumor ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Interferon Type I/genetics ; Interferon Type I/immunology ; Killer Cells, Natural/immunology ; Killer Cells, Natural/pathology ; Lipopeptides/chemistry ; Lipopeptides/pharmacology ; Lymphocyte Activation/drug effects ; Mice ; Mice, Knockout ; Mycoplasma fermentans/chemistry ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/pathology ; Neoplasms, Experimental/therapy ; T-Lymphocytes, Cytotoxic/immunology ; T-Lymphocytes, Cytotoxic/pathology
    Chemical Substances Bacterial Proteins ; Interferon Type I ; Lipopeptides ; macrophage stimulatory lipopeptide 2 (DZX5IUA94D)
    Language English
    Publishing date 2018-03-14
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2018.00496
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The second and third amino acids of Pam2 lipopeptides are key for the proliferation of cytotoxic T cells.

    Takeda, Yohei / Azuma, Masahiro / Hatsugai, Ryoko / Fujimoto, Yukari / Hashimoto, Masahito / Fukase, Koichi / Matsumoto, Misako / Seya, Tsukasa

    Innate immunity

    2018  Volume 24, Issue 5, Page(s) 323–331

    Abstract: ... the proliferative activity of cytotoxic T lymphocytes (CTL) using mouse Ag-presenting dendritic cells (DCs) and OT ...

    Abstract The TLR2 agonist, dipalmitoyl lipopeptide (Pam2LP), has been used as an immune adjuvant without much success. Pam2LP is recognised by TLR2/6 receptors in humans and in mice. This study examined the proliferative activity of cytotoxic T lymphocytes (CTL) using mouse Ag-presenting dendritic cells (DCs) and OT-I assay system, where a library of synthetic Pam2LP was utilised from the Staphylococcus aureus database. Ag-specific CTL expansion and IFN-γ levels largely depended on the Pam2LP peptide sequence. The first Aa is cysteine (Cys), which has an active SH residue to bridge fatty acids, and the second and third Aa are hydrophilic or non-polar. The sequence structurally adapted to the residual constitution of the reported TLR2/6 pocket. The inactive sequence contained proline or leucine/isoleucine after the first Cys. Notably, no direct activation of OT-I cells was detected without DCs by stimulation with the active Pam2LP having the Cys-Ser sequence. MyD88, but not TICAM-1 or IFN pathways, in DCs participates in DC maturation characterised by upregulation of CD40, CD80 and CD86. Hence, the active Pam2LPs appear suitable for dimeric TLR2/6 on DCs, resulting in induction of DC maturation.
    MeSH term(s) Adjuvants, Immunologic ; Animals ; Antigen Presentation ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Cysteine/metabolism ; Dendritic Cells/immunology ; Interferon-gamma/metabolism ; Lipopeptides/genetics ; Lipopeptides/metabolism ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88/genetics ; Myeloid Differentiation Factor 88/metabolism ; Peptide Library ; Protein Conformation ; Serine/metabolism ; Staphylococcus aureus/metabolism ; Staphylococcus aureus/physiology ; T-Lymphocytes, Cytotoxic/immunology ; Toll-Like Receptor 2/agonists
    Chemical Substances Adjuvants, Immunologic ; Lipopeptides ; Myeloid Differentiation Factor 88 ; Pam2CSK4 lipopeptide ; Peptide Library ; Tlr2 protein, mouse ; Toll-Like Receptor 2 ; Serine (452VLY9402) ; Interferon-gamma (82115-62-6) ; Cysteine (K848JZ4886)
    Language English
    Publishing date 2018-05-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2381250-3
    ISSN 1753-4267 ; 1753-4259
    ISSN (online) 1753-4267
    ISSN 1753-4259
    DOI 10.1177/1753425918777598
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Vaccine immunotherapy with ARNAX induces tumor-specific memory T cells and durable anti-tumor immunity in mouse models.

    Takeda, Yohei / Yoshida, Sumito / Takashima, Ken / Ishii-Mugikura, Noriko / Shime, Hiroaki / Seya, Tsukasa / Matsumoto, Misako

    Cancer science

    2018  Volume 109, Issue 7, Page(s) 2119–2129

    Abstract: Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with Toll-like receptor (TLR)3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) ... ...

    Abstract Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with Toll-like receptor (TLR)3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In the present study, 4 different ovalbumin (OVA)-expressing tumor cell lines were implanted into syngeneic mice and subjected to anti-tumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a TLR3-specific agonist that does not activate the mitochondrial antiviral-signaling protein (MAVS) pathway, and thus does not induce systemic inflammation. Dendritic cell priming and proliferative CTL were induced by ARNAX + OVA, but complete remission was achieved only in a PD-L1-low cell line of EG7. Addition of anti-PD-L1 antibody to the ARNAX + OVA therapy brought complete remission to another PD-L1-high subline of EG7. Tumor shrinkage but not remission was observed in MO5 in that regimen. We analyzed tumor cells and tumor-infiltrating immune cells to identify factors associated with successful ARNAX vaccine therapy. Tumors that responded to ARNAX therapy expressed high levels of MHC class I and low levels of PD-L1. The tumor-infiltrating immune cells in ARNAX-susceptible tumors contained fewer immunosuppressive myeloid cells with low PD-L1 expression. Combination with anti-PD-L1 antibody functioned not only within tumor sites but also within lymphoid tissues, augmenting the therapeutic efficacy of the ARNAX vaccine. Notably, ARNAX therapy induced memory CD8
    MeSH term(s) Animals ; Antigens, Neoplasm/immunology ; Disease Models, Animal ; Immunologic Memory/immunology ; Immunotherapy/methods ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes/immunology ; Toll-Like Receptor 3/agonists ; Tumor Microenvironment/immunology
    Chemical Substances Antigens, Neoplasm ; TLR3 protein, mouse ; Toll-Like Receptor 3
    Language English
    Publishing date 2018-06-16
    Publishing country England
    Document type Journal Article
    ZDB-ID 2115647-5
    ISSN 1349-7006 ; 1347-9032
    ISSN (online) 1349-7006
    ISSN 1347-9032
    DOI 10.1111/cas.13649
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Tumoricidal efficacy coincides with CD11c up-regulation in antigen-specific CD8(+) T cells during vaccine immunotherapy.

    Takeda, Yohei / Azuma, Masahiro / Matsumoto, Misako / Seya, Tsukasa

    Journal of experimental & clinical cancer research : CR

    2016  Volume 35, Issue 1, Page(s) 143

    Abstract: ... I interferon (IFN) and interleukin-12 (IL-12), then cross-primes cytotoxic T lymphocytes (CTLs). Proliferation ... T cells, that express CD11c in lymphoid and tumor sites. The numbers of the CD11c(+) CD8(+) T ... cells correlated with those of induced Ag-specific CD8(+) T cells and tumor regression. The CD11c(+) CD8(+) T cell ...

    Abstract Background: Dendritic cells (DCs) mount tumor-associated antigens (TAAs), and the double-stranded RNA adjuvant Poly(I:C) stimulates Toll-like receptor 3 (TLR3) signal in DC, which in turn induces type I interferon (IFN) and interleukin-12 (IL-12), then cross-primes cytotoxic T lymphocytes (CTLs). Proliferation of CTLs correlates with tumor regression. How these potent cells expand with high quality is crucial to the outcome of CTL therapy. However, good markers reflecting the efficacy of DC-target immunotherapy have not been addressed.
    Methods: Using an EG7 (ovalbumin, OVA-positive) tumor-implant mouse model, we examined what is a good marker for active CTL induction in treatment with Poly(I:C)/OVA.
    Results: Simultaneous administration of Poly(I:C) and antigen (Ag) OVA significantly increased a minor population of CD8(+) T cells, that express CD11c in lymphoid and tumor sites. The numbers of the CD11c(+) CD8(+) T cells correlated with those of induced Ag-specific CD8(+) T cells and tumor regression. The CD11c(+) CD8(+) T cell moiety was characterized by its high killing activity and IFN-γ-producing ability, which represent an active phenotype of the effector CTLs. Not only a TLR3-specific (TICAM-1-dependent) signal but also TLR2 (MyD88) signal in DC triggered the expansion of CD11c(+) CD8(+) T cells in tumor-bearing mice. Notably, human CD11c(+) CD8(+) T cells also proliferated in peripheral blood mononuclear cells (PBMC) stimulated with cytomegalovirus (CMV) Ag.
    Conclusions: CD11c expression in CD8(+) T cells reflects anti-tumor CTL activity and would be a marker for immunotherapeutic efficacy in mouse models and probably cancer patients as well.
    MeSH term(s) Animals ; CD11c Antigen/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/transplantation ; Cancer Vaccines/immunology ; Cancer Vaccines/therapeutic use ; Dendritic Cells/immunology ; Gene Expression Regulation, Neoplastic ; Humans ; Immunotherapy ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/therapy ; Ovalbumin/administration & dosage ; Poly I-C/administration & dosage ; Up-Regulation ; Xenograft Model Antitumor Assays
    Chemical Substances CD11c Antigen ; Cancer Vaccines ; Ovalbumin (9006-59-1) ; Poly I-C (O84C90HH2L)
    Language English
    Publishing date 2016-09-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 803138-1
    ISSN 1756-9966 ; 0392-9078
    ISSN (online) 1756-9966
    ISSN 0392-9078
    DOI 10.1186/s13046-016-0416-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Innate-Acquired Linkage in Immunotherapy.

    Seya, Tsukasa

    Cells

    2023  Volume 12, Issue 3

    Abstract: The evolution of the human species is the result of genetic variation [ ... ]. ...

    Abstract The evolution of the human species is the result of genetic variation [...].
    MeSH term(s) Humans ; Immunotherapy ; Immunity, Innate
    Language English
    Publishing date 2023-01-19
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12030371
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Biphasic function of TLR3 adjuvant on tumor and spleen dendritic cells promotes tumor T cell infiltration and regression in a vaccine therapy.

    Azuma, Masahiro / Takeda, Yohei / Nakajima, Hiroko / Sugiyama, Haruo / Ebihara, Takashi / Oshiumi, Hiroyuki / Matsumoto, Misako / Seya, Tsukasa

    Oncoimmunology

    2016  Volume 5, Issue 8, Page(s) e1188244

    Abstract: Successful cancer immunotherapy necessitates T cell proliferation and infiltration into tumor ... whereby Poly(I:C) acts on DC for T cell proliferation and migration remains undetermined ... with tumor-infiltration of CD8(+) T cells. Epitope-specific cytotoxic T lymphocytes (CTLs) were increased ...

    Abstract Successful cancer immunotherapy necessitates T cell proliferation and infiltration into tumor without exhaustion, a process closely links optimal maturation of dendritic cells (DC), and adjuvant promotes this process as an essential prerequisite. Poly(I:C) has contributed to adjuvant immunotherapy that evokes an antitumor response through the Toll-loke receptor 3 (TLR3)/TICAM-1 pathway in DC. However, the mechanism whereby Poly(I:C) acts on DC for T cell proliferation and migration remains undetermined. Subcutaneous injection of Poly(I:C) regressed implant tumors (WT1-C1498 or OVA-EG7) in C57BL/6 mice, which coincided with tumor-infiltration of CD8(+) T cells. Epitope-specific cytotoxic T lymphocytes (CTLs) were increased in spleen by challenge with Poly(I:C)+Db126 WT-1 peptide but not Poly(I:C) alone, suggesting the need of an exogenous Ag density for cross-priming. In tumor, CXCR3 ligands were upregulated by Poly(I:C), which facilitated recruitment of CTL to the tumor. Thus, Poly(I:C) acts on splenic CD8α(+) DC to cross-prime T cells and on intratumor cells to attract CTLs. Besides CD8(+) T cell cross-priming, T cell recruitment into tumor was significantly dampened in Batf3 (-/-) mice, reflecting the importance of tumor Batf3-dependent DC rather than macrophages in T cell recruitment. Poly(I:C)-induced XCR1(hi) CD8α(+) DC with high TLR3 levels were markedly decreased in Batf3 (-/-) mice, which hampered the production of IL-12 and IL-12-mediated CD4(+)/CD8(+) T cell proliferation. Subcutaneous administration of Poly(I:C) and adoptive transfer of wild-type CD8α(+) DC largely recovered antitumor response in those Batf3 (-/-) mice. Collectively, Poly(I:C) tunes up proper maturation of CD8α(+) DC to establish TLR3-mediated IL-12 function and cross-presentation in spleen and lymphocyte-attractive antitumor microenvironment in tumor.
    Language English
    Publishing date 2016-05-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-4011
    ISSN (online) 2162-402X
    ISSN 2162-4011
    DOI 10.1080/2162402X.2016.1188244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Toll-like receptor 2 ligand and interferon-γ suppress anti-tumor T cell responses by enhancing the immunosuppressive activity of monocytic myeloid-derived suppressor cells.

    Shime, Hiroaki / Maruyama, Akira / Yoshida, Sumito / Takeda, Yohei / Matsumoto, Misako / Seya, Tsukasa

    Oncoimmunology

    2017  Volume 7, Issue 1, Page(s) e1373231

    Abstract: ... ...

    Abstract CD11b
    Language English
    Publishing date 2017-09-21
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2645309-5
    ISSN 2162-402X ; 2162-4011
    ISSN (online) 2162-402X
    ISSN 2162-4011
    DOI 10.1080/2162402X.2017.1373231
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Dendritic cells from oral cavity induce Foxp3(+) regulatory T cells upon antigen stimulation.

    Yamazaki, Sayuri / Maruyama, Akira / Okada, Kohei / Matsumoto, Misako / Morita, Akimichi / Seya, Tsukasa

    PloS one

    2012  Volume 7, Issue 12, Page(s) e51665

    Abstract: ... Foxp3(+)CD4(+) regulatory T cells (T-regs) and regulate immunity versus tolerance in the intestines ... we report that DCs from the oral cavity induce Foxp3(+) T-regs as well as DCs from intestine. We found ... that oral-cavity-draining cervical lymph nodes contained higher frequencies of Foxp3(+) T-regs and ROR-γt ...

    Abstract Evidence is accumulating that dendritic cells (DCs) from the intestines have the capacity to induce Foxp3(+)CD4(+) regulatory T cells (T-regs) and regulate immunity versus tolerance in the intestines. However, the contribution of DCs to controlling immunity versus tolerance in the oral cavity has not been addressed. Here, we report that DCs from the oral cavity induce Foxp3(+) T-regs as well as DCs from intestine. We found that oral-cavity-draining cervical lymph nodes contained higher frequencies of Foxp3(+) T-regs and ROR-γt(+) CD4(+)T cells than other lymph nodes. The high frequency of Foxp3(+) T-regs in the oral-cavity-draining cervical lymph nodes was not dependent on the Toll like receptor (TLR) adaptor molecules, Myd88 and TICAM-1 (TRIF). In contrast, the high frequency of ROR-γt(+) CD4(+)T cells relies on Myd88 and TICAM-1. In vitro data showed that CD11c(+) DCs from oral-cavity-draining cervical lymph nodes have the capacity to induce Foxp3(+) T-regs in the presence of antigen. These data suggest that, as well as in the intestinal environment, antigen-presenting DCs may play a vital role in maintaining tolerance by inducing Foxp3(+) T-regs in the oral cavity.
    MeSH term(s) Adaptor Proteins, Vesicular Transport/biosynthesis ; Animals ; Antigens/immunology ; Antigens/metabolism ; CD4-Positive T-Lymphocytes/cytology ; Coculture Techniques ; Cytokines/metabolism ; Dendritic Cells/cytology ; Dendritic Cells/immunology ; Forkhead Transcription Factors/metabolism ; Humans ; Immune Tolerance/immunology ; Interleukin-2 Receptor alpha Subunit/biosynthesis ; Intestines/immunology ; Lymph Nodes/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mouth/immunology ; Myeloid Differentiation Factor 88/biosynthesis ; Signal Transduction ; Spleen/metabolism ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances Adaptor Proteins, Vesicular Transport ; Antigens ; Cytokines ; FOXP3 protein, human ; Forkhead Transcription Factors ; Interleukin-2 Receptor alpha Subunit ; MYD88 protein, human ; Myeloid Differentiation Factor 88 ; TICAM-1 protein, mouse
    Language English
    Publishing date 2012-12-18
    Publishing country United States
    Document type Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0051665
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: IL-6 and IFN-alpha from dsRNA-stimulated dendritic cells control expansion of regulatory T cells.

    Kubota, Nobuhiko / Ebihara, Takashi / Matsumoto, Misako / Gando, Satoshi / Seya, Tsukasa

    Biochemical and biophysical research communications

    2010  Volume 391, Issue 3, Page(s) 1421–1426

    Abstract: Foxp3(+)CD4(+) regulatory T cells (Treg) control not only autoimmunity but also the effective ...

    Abstract Foxp3(+)CD4(+) regulatory T cells (Treg) control not only autoimmunity but also the effective immune response against RNA virus infections, which produces virus-derived double-stranded RNA (dsRNA). To induce effective anti-viral immunity, it is a key issue to learn how Treg respond to dsRNA in vitro and in vivo. We here showed that synthetic dsRNA, polyI:C, caused peripheral expansion of functional Treg in a TICAM-1- and IL-6-dependent manner in vivo. PolyI:C did not expand Treg directly, but promoted the expansion of naturally occurring Treg indirectly through IL-6 produced from dendritic cells (DCs). In addition, the expansion of Treg by IL-6 was inhibited by IFN-alpha from polyI:C-stimulated DCs. These data suggest that the balance of IL-6 and IFN-alpha in the region of RNA virus infection may determine the number of peripheral Treg, which affects the effective immune responses against viruses.
    MeSH term(s) Adaptor Proteins, Vesicular Transport/genetics ; Adaptor Proteins, Vesicular Transport/metabolism ; Animals ; Bone Marrow Cells/cytology ; Bone Marrow Cells/immunology ; Cell Proliferation ; Cells, Cultured ; Dendritic Cells/immunology ; Interferon-alpha/genetics ; Interferon-alpha/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Lymphocyte Activation ; Mice ; Mice, Mutant Strains ; Poly C/immunology ; Poly C/pharmacology ; RNA, Double-Stranded/immunology ; RNA, Double-Stranded/pharmacology ; RNA, Viral/immunology ; Rats ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology
    Chemical Substances Adaptor Proteins, Vesicular Transport ; Interferon-alpha ; Interleukin-6 ; RNA, Double-Stranded ; RNA, Viral ; TICAM-1 protein, mouse ; Poly C (30811-80-4)
    Language English
    Publishing date 2010-01-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 205723-2
    ISSN 1090-2104 ; 0006-291X ; 0006-291X
    ISSN (online) 1090-2104 ; 0006-291X
    ISSN 0006-291X
    DOI 10.1016/j.bbrc.2009.12.081
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: PolyI:C and mouse survivin artificially embedding human 2B peptide induce a CD4+ T cell response to autologous survivin in HLA-A*2402 transgenic mice.

    Kasamatsu, Jun / Takahashi, Shojiro / Azuma, Masahiro / Matsumoto, Misako / Morii-Sakai, Akiko / Imamura, Masahiro / Teshima, Takanori / Takahashi, Akari / Hirohashi, Yoshihiko / Torigoe, Toshihiko / Sato, Noriyuki / Seya, Tsukasa

    Immunobiology

    2015  Volume 220, Issue 1, Page(s) 74–82

    Abstract: CD4(+) T cell effectors are crucial for establishing antitumor immunity. Dendritic cell maturation ... by immune adjuvants appears to facilitate subset-specific CD4(+) T cell proliferation, but the adjuvant ... effect for CD4 T on induction of cytotoxic T lymphocytes (CTLs) is largely unknown. Self-antigenic ...

    Abstract CD4(+) T cell effectors are crucial for establishing antitumor immunity. Dendritic cell maturation by immune adjuvants appears to facilitate subset-specific CD4(+) T cell proliferation, but the adjuvant effect for CD4 T on induction of cytotoxic T lymphocytes (CTLs) is largely unknown. Self-antigenic determinants with low avidity are usually CD4 epitopes in mutated proteins with tumor-associated class I-antigens (TAAs). In this study, we made a chimeric version of survivin, a target of human CTLs. The chimeric survivin, where human survivin-2B containing a TAA was embedded in the mouse survivin frame (MmSVN2B), was used to immunize HLA-A-2402/K(b)-transgenic (HLA24(b)-Tg) mice. Subcutaneous administration of MmSVN2B or xenogeneic human survivin (control HsSNV2B) to HLA24(b)-Tg mice failed to induce an immune response without co-administration of an RNA adjuvant polyI:C, which was required for effector induction in vivo. Although HLA-A-2402/K(b) presented the survivin-2B peptide in C57BL/6 mice, 2B-specific tetramer assays showed that no CD8(+) T CTLs specific to survivin-2B proliferated above the detection limit in immunized mice, even with polyI:C treatment. However, the CD4(+) T cell response, as monitored by IFN-γ, was significantly increased in mice given polyI:C+MmSVN2B. The Th1 response and antibody production were enhanced in the mice with polyI:C. The CD4 epitope responsible for effector function was not Hs/MmSNV13-27, a nonconserved region between human and mouse survivin, but region 53-67, which was identical between human and mouse survivin. These results suggest that activated, self-reactive CD4(+) helper T cells proliferate in MmSVN2B+polyI:C immunization and contribute to Th1 polarization followed by antibody production, but hardly participate in CTL induction.
    MeSH term(s) Amino Acid Sequence ; Animals ; Antibody Formation ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Epitopes, T-Lymphocyte/chemistry ; Epitopes, T-Lymphocyte/genetics ; Epitopes, T-Lymphocyte/immunology ; Exons ; Gene Expression ; Gene Order ; Genetic Loci ; HLA-A24 Antigen/genetics ; Humans ; Inhibitor of Apoptosis Proteins/genetics ; Inhibitor of Apoptosis Proteins/immunology ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; Open Reading Frames ; Peptide Fragments/genetics ; Peptide Fragments/immunology ; Poly I-C/immunology ; Recombinant Fusion Proteins/chemistry ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/immunology ; Repressor Proteins/genetics ; Repressor Proteins/immunology
    Chemical Substances BIRC5 protein, human ; Birc5 protein, mouse ; Epitopes, T-Lymphocyte ; HLA-A*24:02 antigen ; HLA-A24 Antigen ; Inhibitor of Apoptosis Proteins ; Peptide Fragments ; Recombinant Fusion Proteins ; Repressor Proteins ; Poly I-C (O84C90HH2L)
    Language English
    Publishing date 2015-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 563292-4
    ISSN 1878-3279 ; 0171-2985
    ISSN (online) 1878-3279
    ISSN 0171-2985
    DOI 10.1016/j.imbio.2014.08.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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