Identification of Th cells in vivo and analysis of differentiation and function of Th2 cells by costimulatory molecules
| Project/Area Number |
16616008
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
アレルギー
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
AKIBA Hisaya Juntendo University, Immunology, Assistant Prof., 医学部, 講師 (60338316)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | T cell differentiation / ICOS / B7RP-1 / OX40 / OX40L / CXCR5 / monoclonal antibody / Th1 / Th2 / Tim / Tim ligand / Tim family / 喘息疾患 |
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| Research Abstract |
1. ICOS is a new member of the CD28 family of costimulatory molecules that is expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on B cells. Although the blockade of ICOS/B7RP-1 interaction inhibits T cell-dependent Ab production and germinal center formation, the mechanism remains unclear. We speculated that the ICOS/B7RP-1 interaction might be required to up-regulate the expression of a chemokine receptor CXCR5 on CD4 T cells. CXCR5 confers responsiveness to B lymphocyte chemokine (CXCL13). A subset of CD4^+ T cells also express CXCR5, which mediates their migration to the B cell follicles where they provide cognate help to B cells. Thus, CXCR5^+ CD4^+ T cells are referred to as follicular helper T (Th) cells. Previous studies have implicated OX40/OX40 ligand (OX40L) interaction, a pair of the TNFR/TNF family members, in the expression of CXCR5 on CD4^+ T cells. Therefore, we compared the contributions of ICOS/B7RP-1 and OX40/OX40L to the development of CXC
… More
R5^+ CD4^+ follicular Th cells and GC B cells. Our results indicated that the ICOS/B7RP-1 interaction plays an essential role of follicular Th cells in the spleen and lymph nodes, but the GC formation in lymph nodes is not always dependent on follicular Th cells. On the other hand, a substantial contribution of OX40/OX40L interaction to the development of follicular Th cells and GC B cells was observed only in lymph nodes of certain strains of mice, depending on differential expression of OX40 on follicular Th cells. We also found sub-populations of activated CD4^+ T cells (CXCR5^+ ICOS^+ OX40^- cells, CXCR5^- ICOS^+ OX40^- cells, CXCR5^- ICOS^- OX40^+ cells, and CXCR5^- ICOS^+ OX40^+ cells) in the spleen and LN. It is possible that the three CXCR5^- populations may represent functionally distinct subsets producing Th1 or Th2 cytokines in vivo.
2. We demonstrated that IOCS play a role as costimulatory molecules in NKT cell activation, which augments cytokines production and cytotoxic activity. Less
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Immune responses against a single CD8+-T-cell epitope induced by virus vector vaccination can successfully control Trypanosoma cruzi infection.2005
Author(s)
Miyahira, Y., Y.Takashima, S.Kobayashi, Y.Matsumoto, T.Takeuchi, M.Ohyanagi-Hara, A.Yoshida, A.Ohwada, H.Akiba, H.Yagita, K.Okumura, H.Ogawa.
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Journal Title
Infect Immun 73
Pages: 7356-7365
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo.2005
Author(s)
Akiba, H., K.Takeda, Y.Kojima, Y.Usui, N.Harada, T.Yamazaki, J.Ma, K.Tezuka, H.Yagita, K.Okumura.
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Journal Title
J Immunol 175
Pages: 2340-2348
Description
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[Journal Article] Regulation of murine chronic colitis by CD4+CD25- programmed death-1+ T cells2005
Author(s)
Totsuka, T., T.Kanai, S.Makita, R.Fujii, Y.Nemoto, S.Oshima, R.Okamoto, A.Koyanagi, H.Akiba, K.Okumura, H.Yagita, M.Watanabe.
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Journal Title
Eur J Immunol 35
Pages: 1773-1785
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] IFN-gamma-mediated negative feedback regulation of NKT-cell function by CD94/NKG2.2005
Author(s)
Ota, T., K.Takeda, H.Akiba, Y.Hayakawa, K.Ogasawara, Y.Ikarashi, S.Miyake, H.Wakasugi, T.Yamamura, M.Kronenberg, D.H.Raulet, K.Kinoshita, H.Yagita, M.J.Smyth, K.Okumura.
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Journal Title
Description
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[Journal Article] ICOS costimulates invariant NKT cell activation.2005
Author(s)
Kaneda, H., K.Takeda, T.Ota, Y.Kaduka, H.Akiba, Y.Ikarashi, H.Wakasugi, M.Kroneneberg, K.Kinoshita, H.Yagita, K.Okumura.
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Journal Title
Biochem Biophys Res Commun 327
Pages: 201-207
Description
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[Journal Article] TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver.2005
Author(s)
Takeda, K., E.Cretney, Y.Hayakawa, T.Ota, H.Akiba, K.Ogasawara, H.Yagita, K.Kinoshita, K.Okumura, M.J.Smyth.
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Journal Title
Blood 105
Pages: 2082-2089
Description
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[Journal Article] Blockade of 4-1BB (CD137)/4-1BB ligand interactions increases allograft survival.2004
Author(s)
Cho, H.R., B.Kwon, H.Yagita, S.La, E.A.Lee, J.E.Kim, H.Akiba, J.Kim, J.H.Suh, D.S.Vinay, S.A.Ju, B.S.Kim, R.S.Mittler, K.Okumura, B.S.Kwon.
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Journal Title
Transpl Int 17
Pages: 351-361
Description
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[Journal Article] Induction of tumor-specific T cell immunity by anti-DR5 antibody therapy.2004
Author(s)
Takeda, K., N.Yamaguchi, H.Akiba, Y.Kojima, Y.Hayakawa, J.E.Tanner, T.J.Sayers, N.Seki, K.Okumura, H.Yagita, M.J.Smyth.
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Journal Title
J Exp Med 199
Pages: 437-448
Description
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[Journal Article] B7-DC regulates asthmatic response by an IFN-gamma-dependent mechanism.2004
Author(s)
Matsumoto, K., H.Inoue, T.Nakano, M.Tsuda, Y.Yoshiura, S.Fukuyama, F.Tsushima, T.Hoshino, H.Aizawa, H.Akiba, D.Pardoll, N.Hara, H.Yagita, M.Azuma, Y.Nakanishi.
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Journal Title
J Immunol 172
Pages: 2530-2541
Description
「研究成果報告書概要(欧文)」より
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