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実験免疫学

Experimental Immunology

TEL 06-6879-4462

FAX 06-6879-4464

研究者ウェブサイト

概要

正常な免疫系は、病原微生物などに反応し、これを排除するが、正常な自己組織には反応しない。もしリンパ球が正常な自己抗原に反応し組織を破壊すれば、関節リウマチ、若年性糖尿病などの自己免疫病となる。この自己に対する免疫不応答、即ち、免疫自己寛容が、正常個体でどのように確立され、どのように維持されるか、の理解は、自己免疫病の原因・発症機構の理解とその治療・予防に留まらない。自己組織から発生した癌細胞に対する効果的な免疫応答の惹起法、さらには、他人からの移植臓器をあたかも自己組織として安定に受容させる方法の開発に繋がる。また、花粉など生体に無害な物質に対する過剰反応であるアレルギーの制御に繋がる。

当研究室では、このような免疫自己寛容の重要な機序として、正常個体中に存在し、自己と反応するリンパ球の活性化・増殖を抑制する内在性制御性T細胞を発見し、研究している。抑制機能をもつT細胞が存在するか否かについては免疫学者の間で長年にわたり議論があった。私たちは、それが機能的、発生的に特異なT細胞群であり、その異常は免疫自己寛容を破綻させ、自己免疫病の原因となることを実験的に証明した。また、この内在性制御性T細胞の減少、機能の減弱によって有効な腫瘍免疫を誘導でき、逆に、制御性T細胞を強化すれば移植臓器に対する安定な免疫寛容が誘導可能であることを実験的に示した。さらに、自己免疫病、アレルギー、炎症性腸疾患を伴うヒトの遺伝性免疫疾患のひとつが、内在性制御性T細胞の発生・機能のマスター制御遺伝子Foxp3の異常によることを証明し、制御性T細胞の異常がヒトの免疫疾患の直接的原因となる可能性を明確に示した。同時に、この細胞群の発生・機能を細胞、遺伝子レベルで操作し、自己免疫病、アレルギーなどの免疫疾患の治療に応用できる可能性を開いた。制御性T細胞の研究は、ここ数年、自己免疫疾患、アレルギー、慢性感染症、臓器移植、癌免疫などの病的、生理的免疫応答の制御を目指して、世界中で活発、急速な進展をみせている。制御性T細胞の広汎な医療応用を目指して活発な研究を展開したいと考えている。

当研究室のもうひとつの研究テーマは、自己免疫病、特に関節リウマチの研究である。私たちの樹立したSKGマウスは、ヒトの関節リウマチと酷似した自己免疫性関節炎を自然発症する。その原因は、T細胞シグナル分子ZAP70の一塩基突然変異であり、その結果、胸腺でのT細胞選択機構が変化し、関節炎惹起性T細胞が産生される。このようなシグナル伝達の遺伝子異常が、どのようにして特定の自己免疫病を発症させるに到るかを解明したいと考えている。

いずれの研究テーマも、基礎的には、免疫寛容の分子、細胞機構の解明、応用としては、生理的、病的免疫応答の制御法の開発が目的である。

主任研究者

坂口 志文 教授

研究内容

免疫寛容の導入・維持機構、特に制御性T細胞の役割に関する研究

学歴

1976 京都大学医学部卒業
1983 京都大学医学部博士号取得

職歴

1999 京都大学再生医科学研究所生体機能調節学分野教授
2007 京都大学再生医科学研究所 所長
2011 大阪大学免疫学フロンティア研究センター実験免疫学分野教授
2013 大阪大学特別教授

受賞・表彰

2003.11 持田記念学術賞
2004.6 Cancer Research Institute's 2004 William B. Coley Award for Distinguished Research in Basic and Tumor Immunology
2005.11 武田医学賞
2005.12 高峰記念三共賞
2007.4 文部科学大臣表彰科学技術賞
2008.3 上原賞
2008.11 慶應医学賞
2009.11 紫綬褒章
2012.1 朝日賞
2012.3 日本学士院賞
2012.5 米国National Academy of Sciences外国人会員
2015.1 Maharshi Sushruta Award
2015.3 Gairdner International Award
2015.5 中日文化賞
2015.9 トムソン・ロイター引用栄誉賞
2017.1 クラフォード賞
2017.10 文化功労者顕彰
2018.3 安藤百福賞
2019.6 第2回山田和彦賞
2019.9 ドイツ免疫学会賞
2019.11 文化勲章
2020.01 パウル・エールリヒ&ルートヴィヒ・ダルムシュテッター賞
2020.06 ロベルト・コッホ賞

メンバー

  • 坂口 志文 教授
    shimonifrec.osaka-u.ac.jp
  • 大倉 永也　教授
    nohkuraifrec.osaka-u.ac.jp
  • 田中 淳　准教授
    atanakaifrec.osaka-u.ac.jp
  • 坂口 教子　招へい教員
    norikosifrec.osaka-u.ac.jp
  • 三上 統久　准教授
    mikamiifrec.osaka-u.ac.jp
  • 市山 健司　准教授
    ichikenifrec.osaka-u.ac.jp

業績

論文

  • Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M, Saito T, Nishioka M, Wing JB, Adeegbe D, Katayama I, Sakaguchi S. Detection of self-reactive CD8+ T cells with an anergic phenotype in healthy individuals. Science. 346:1536-1540, 2014.
  • Ito Y, Hashimoto M, Hirota K, Ohkura N, Morikawa H, Nishikawa H, Tanaka A, Furu M, Ito H, Fujii T, Nomura T, Yamazaki S, Morita A, Vignali DA, Kappler JW, Matsuda S, Mimori T, Sakaguchi N, Sakaguchi S. Detection of T-cell responses to a ubiquitous cellular protein in autoimmune disease. Science. 346:363-368, 2014.
  • Wing JB, Ise W, Kurosaki T, Sakaguchi S. Regulatory T-cells control antigen-specific expansion of Tfh cell number and humoral immune responses via the coreceptor CTLA-4. Immunity. 41:1013-1025,2014.
  • Yamazaki S, Nishioka A, Kasuya S, Ohkura N, Hemmi H, Kaisho T, Taguchi O, Sakaguchi S, Morita A. Homeostasis of Thymus-Derived Foxp3+ Regulatory T Cells Is Controlled by Ultraviolet B Exposure in the Skin. J Immunol. 193:5488-5497, 2014 .
  • Kitagawa Y, Ohkura N, Sakaguchi S. Epigenetic control of thymic Treg-cell development. Eur. J. Immunol. 2014 Oct 28.
  • Morikawa H, Ohkura N, Vandenbon A, Itoh M, Nago-Sato S, Kawaji H, Lassmann T, Carninci P, Hayashizaki Y, Forrest A, Standley D, Date D, Sakaguchi S, and the FANTOM consortium. Differential roles of epigenetic changes and Foxp3 expression in regulatory T cell-specific transcriptional regulation. PNAS. 111: 5289-5294, 2014.
  • Mikami N, Sakaguchi S. CD28 signals the differential control of regulatory T cells and effector T cells. Eur J Immunol. 44:955-957, 2014.
  • Miyara M, Ito Y, Sakaguchi S. TREG-cell therapies for autoimmune rheumatic diseases. Nat Rev Rheumatol. 10:543-551 2014.
  • Morikawa H, Sakaguchi S. Genetic and epigenetic basis of Treg cell development and function: From a FoxP3-centered view to an epigenome-defined view of natural Treg cells. Immunol. Rev. 259: 192-205, 2014.
  • Forrest A, ..., Morikawa H., ..., Hamaguchi M., ..., Ohkura N., ...,Sakaguchi S., ...,Hayashizaki Y, et al., A promoter level mammalian expression atlas. Nature. 507: 462-470, 2014.
  • Wing JB, Sakaguchi S. Foxp3+ Treg cells in humoral immunity. Int Immunol. 26: 61-69, 2014.
  • Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol. 27: 1-7, 2014.
  • Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, Ezoe S, Kanakura Y, Sato E, Fukumori Y, Karbach J, Jager E, and Sakaguchi S. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking anti-tumor immune responses in humans. PNAS. 110:17945-17950, 2013.
  • Atarashi K, Tanoue T, Oshima K, Suda W, Nagano Y, Nishikawa H, Fukuda S, Saito T, Narushima S, Hase K, Kim S, Fritz JV, Wilmes P, Ueha S, Matsushima K, Ohno H, Olle B, Sakaguchi S, Taniguchi T, Morita H, Hattori M, Honda K. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 500:232-236, 2013.
  • Ohkura N, Kitagawa Y, Sakaguchi S. Development and Maintenance of Regulatory T cells. Immunity.38:414-423, 2013.
  • Yamaguchi T, Kishi A, Osaki M, Morikawa H, Prieto-Martin P, Wing K, Saito T, and Sakaguchi S. Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression. PNAS, 110(23):E2116-2125, 2013.
  • Sakaguchi S, Vignali DAA, Niec, RE, Rudensky AY, and Waldmann H. Regulatory T cell plasticity and stability. Nat. Rev. Immunol. 13:461-467, 2013.
  • Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DA, Ziegler SF. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol. 14:307-308, 2013.
  • Ohkura N, Sakaguchi S. Treg cells acquire new directions, cytokines navigate. Immunity. 37:443-4, 2012.
  • Ohkura N, Hamaguchi M, Morikawa H, Sugimura K, Tanaka A, Ito Y, Osaki M, Tanaka Y, Yamashita R, Nakano N, Huehn J, Fehling HJ, Sparwasser T, Nakai K, Sakaguchi S. T cell receptor stimulation-induced epigenetic changes and foxp3 expression are independent and complementary events required for Treg cell development. Immunity. 37:785-99, 2012.
  • Noguchi, T., Kato, T., Wang, L., Maeda, Y., Ikeda, H., Sato, E., Knuth, A., Gnjatic, S., Ritter, G., Sakaguchi, S., Old, L. J., Shiku, H., and Nishikawa, H. Intracellular tumor-associated antigens represent effective targets for passive immunotherapy. Cancer Res. 72:1672-1682, 2012.
  • Hamaguchi M, Sakaguchi S. Regulatory T cells expressing PPAR-γ control inflammation in obesity. Cell Metab. 16:4-6, 2012.
  • Wing JB, Sakaguchi S. Multiple treg suppressive modules and their adaptability. Front Immunol. 3:178. Epub 2012.
  • Nishikawa, H., Maeda, Y., Ishida, T., Gnjatic, S., Sato, E., Mori, F., Sugiyama, D., Ito, A., Fukumori, Y., Utsunomiya, A., Inagaki, H., Old, L. J., Ueda, R., and Sakaguchi, S. Cancer/testis antigens are novel targets of immunotherapy for adult T-cell leukemia/lymphoma. Blood. 119:3097-3104, 2012.
  • Sakaguchi, S., Benham, H., Cope, A. P., Thomas, R. T-cell receptor signaling and the pathogenesis of autoimmune arthritis: insights from mouse and man. Immunol Cell Biol. 90:277-87, 2012.
  • Sakaguchi, S., Powrie, F., Ransohoff, R. M. Re-establishing immunological self-tolerance in autoimmune disease. Nat Med. 18:54-58, 2012.
  • Ohe, H., Waki, K., Yoshitomi, M., Morimoto, T., Nafady-Hego, H., Satoda, N., Li, Y., Zhao, X., Sakaguchi, S., Uemoto, S., Bishop, G. A., Koshiba, T. Factors affecting operational tolerance after pediatric living-donor liver transplantation: impact of early post-transplant events and HLA match. Transpl Int. 25:97-106, 2012.
  • Yoshioka, Y., Ono, M., Osaki, M., Konishi, I., Sakaguchi, S. Differential effects of inhibition of bone morphogenic protein (BMP) signalling on T-cell activation and differentiation. Eur J Immunol. 42:749-759, 2012.
  • Wing, K., Yamaguchi, T., Sakaguchi, S. Cell-autonomous and ?nonautonomous functions of CTLA-4 for negative control of immune responses. Trends Immunol. 32:428-433, 2011.
  • Sakaguchi, S., Wing K. Damping by depletion. Science. 332:542-543, 2011.
  • Ohkura, N., Sakaguchi, S. Maturation of effector regulatory T cells. Nat Immunol. 12:283-284, 2011.
  • Yamaguchi, T., Wing, J. B., Sakaguchi, S. Two modes of immune suppression by Foxp3(+) regulatory T cells under inflammatory or non-inflammatory conditions. Semin Immunol. 23:424-430, 2011.
  • Sakaguchi, S., Tanaka, S., Tanaka, A., Ito, Y., Maeda, S., Sakaguchi, N., Hashimoto, M. Thymus, innate immunity and autoimmune arthritis: interplay of gene and environment. FEBS Lett. 585:3633-3639, 2011.
  • Wing, J. B., Sakaguchi, S. TCR diversity and Treg cells, sometimes more is more. Eur J Immunol. 41:3097-3100, 2011.
    Ohkura, N., Hamaguchi, M., Sakaguchi, S. FOXP3(+) regulatory T cells: control of FOXP3 expression by pharmacological agents. Trends Pharmacol. Sci. 32:158-66, 2011.
  • Ohe, H., Li, Y., Nafady-Hego, H., Kayo, W., Sakaguchi, S., Wood, K., Calne, R., Uemoto, S., Koshiba, T. Minimal but essential doses of immunosuppression: A more realistic approach to improve long-term outcomes for pediatric living-donor liver transplantation. Transplantation. 91:808-810, 2011.
  • Satou, Y., Yasunaga, J., Zhao, T., Yoshida, M., Miyazato, P., Takai, K., Shimizu, K., Ohshima, K., Green, P. L., Ohkura, N., Yamaguchi, T., Ono, M., Sakaguchi, S., Matsuoka, M. HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo. PLoS Pathog. 7(2):e1001274, 2011.
  • Miyara, M., Gorochov, G., Ehrenstein, M., Musset, L., Sakaguchi, S., Amoura, Z. Human FoxP3(+) regulatory T cells in systemic autoimmune diseases. Autoimmun. Rev. 10:744-755, 2011.
  • Miyara, M., and Sakaguchi, S. FoxP3+CD4+ regulatory T cells: their knowns and unknowns. Immunol. Cell. Biology. 89:346-351, 2011.
  • Sakaguchi, S. Regulatory T cells: history and perspective. Methods in Molecular Biology. 77: 1-13, 2011.
  • Ohkura N, Sakaguchi S. Foxo1 and Foxo3 help Foxp3. Immunity. 33:835-7, 2010.
  • Fujii, H., Arakawa, A., Kitoh, A., Miyara, M., Kato, M., Kore-Eda, S., Sakaguchi, S., Miyachi, Y., Tanioka, M., and Ono, M. Perturbations of both non-regulatory and regulatory FOXP3(+) T cells in patients with malignant melanoma. Br. J. Dermatol. 164:1052-1060, 2010.
  • Sakaguchi, S. Conditional stability of T cells. Nature. 468:4142, 2010.
  • Nafady-Hego, H., Li, Y., Ohe, H., Zhao, X., Satoda, N., Sakaguchi, S., Wood, K., Uemoto, S., and Koshiba, T. The generation of donor-specific CD4+CD25++CD45RA+ naive regulatory T cells in operationally tolerance patients after pediatric living-donor liver transplantation. Transplantation. 90:1547-55, 2010.
  • Mitsui, J., Nishikawa, H., Muraoka, D., Wang, L., Noguchi, T., Sato, E., Kondo, S., Allison, J. P., Sakaguchi, S., Old, L. J., Kato, T., and Shiku, H. Two distinct mechanisms of augmented antitumor activity by modulation of immunostimulatory/inhibitory signals. Clin. Cancer Res. 16:2781-91, 2010.
  • Nishikawa, H., and Sakaguchi, S. Regulatory T cells in tumor immunity. Int. J. Cancer. 127:759-67, 2010.
  • Ohkura, N., and Sakaguchi, S. Regulatory T cells: roles of Tcell erceptor for their development and function. Semin. Immunopathol. 32:95-106, 2010.
  • Sakaguchi, S., Miyara, M., Costantino, C. M., and Hafler, D. A. FOXP3+ regulatory T cells in the human system. Nat. Rev. Immunol. 185:2295-305, 2010.
  • Hashimoto, M., Hirota, K., Yoshitomi, H., Maeda, S., Teradaira, S., Akizuki, S., Prieto-Martin, P., Nomura, T., Sakaguchi, N., Kohl, J., Heyman, B., Takahashi, M., Fujita, T., Mimori, T., Sakaguchi, S. Complement drives Th-17 cell differentiation and triggers autoimmune disease. J. Exp. Med. 207:1135-43, 2010.
  • Tanaka, S., Maeda, S., Hashimoto. M., Teradaira, S., Hirota,K., Yoshitomi, H., Katakai, T., Shimizu, A., Nomura, T., Sakaguchi, N., and Sakaguchi, S. Graded attenuation of TCR signaling elicits distinct autoimmune diseases by altering thymic T cell selection and regulatory T cell function. J. Immunol. 185:2295-305, 2010.
  • Wing, K., and Sakaguchi, S. Regulatory T cells exert checks and balances on self-tolerance and autoimmunity. Nat. Immunol. 11:7-13, 2010.
  • Sakaguchi S, Wing K, Onishi Y, Prieto-Martin P, Yamaguchi T. Regulatory T cells: how do they suppress immune responses? Int. Immunol. 21:1105-11, 2009.
  • Kitoh, A., Ono, M., Naoe, Y., Ohkura, N., Yamaguchi, T, Yaguchi, H., Kitabayashi, I., Tsukada, T., Nomura, T., Miyachi,Y., Taniuchi, I., and Sakaguchi, S. Indispensable role of Runx1/Cbfb complexes for in vivo suppressive function of FoxP3+ regulatory T cells. Immunity. 31:609-620, 2009.
  • Sakaguchi, S., Wing, K., and Yamaguchi, T. Dynamics of peripheral tolerance and immune regulation. Eur. J. Immunol. 39(9):2331-6, 2009.
  • Ito Y, Usui T, Kobayashi S, Iguchi-Hashimoto M, Ito H, Yoshitomi H, Nakamura T, Shimizu M, Kawabata D, Yukawa N, Hashimoto M, Sakaguchi N, Sakaguchi S, Yoshifuji H, Nojima T, Ohmura K, Fujii T, Mimori T. Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis. Arthritis Rheum. 60:2294-2303, 2009.
  • Miyara, M., Wing, K., and Sakaguchi, S. Therapeutic approaches to allergy and autoimmunity based on FoxP3+ regulatory T-cell activation and expansion. J Allergy Clin Immunol. 123:749-55, 2009.
  • Ohkura, N,. and Sakaguchi, S. A novel modifier of regulatory T cells Nat Immunol. 10: 685-686, 2009.
  • Miyara, M., Shima, T., Kitoh, A., Yoshioka, Y., Niwa, A., Taflin, C., Heike, T., Valeyre, D., Mathian, A., Nakahata, T., Yamaguchi T., Nomura, T., Wing, K., Ono, M., Amoura, Z., Guy Gorochov, G., and Sakaguchi, S. Functional delineation and differentiation dynamics of human CD4(+) T cells expressing the FoxP3 transcription factor. Immunity. 30:899-911, 2009.
  • Nagahama, K., Fehervari, Z., Oida, T., Ogawa, O., and Sakaguchi, S. Differential control of alloantigen-specific regulatory T cells and effector T cells by anti-CD4 and other agents in establishing transplantation tolerance. Int.Immunol. 21:379-391, 2009.
  • Yoshitomi, M., Koshiba, T., Haga, H., Li, Y., Zhao, X., Cheng, D., Miyagawa, A., Sakashita, H., Tsuruyama T., Ueda, M., Wood, K., Sakaguchi S., Manabe, T., Tanaka, K., and Uemoto, S. Requirement of protocol biopsy before and after complete cessation of immunosuppression following liver transplantation. Transplantation. 87:606-614, 2009.
  • Wing K, and Sakaguchi S. Regulatory T cells. In Clinical Immunology, eds. R. R. Rich, T. A. Fleisher, W. T. Shearer, H. W. Schroeder, Jr., A. J. Frew, and C. M. Weyand, Mosby. 2008; P249-258.
  • Miyara, M., and Sakaguchi, S. Regulatory T Cells and the Control of Auto-Immunity: From day 3 Thymectomy to FoxP3+ Regulatory T Cells. In Regulatory T cells and Clinical Application, Ed. S. Jiang, Springer, p3-16, 2008.
  • Sakihama T, Sato T, Iwanari H, Kitamura T, Sakaguchi S, Kodama T, Hamakubo T. A simple detection method for low-affinity membrane protein interactions by baculoviral display. PLoS ONE. 2008;3(12):e4024.
  • Satoda N, Shoji T, Wu Y, Fujinaga T, Chen F, Aoyama A, Zhang JT, Takahashi A, Okamoto T, Matsumoto I, Sakai H, Li Y, Zhao X, Manabe T, Kobayashi E, Sakaguchi S, Wada H, Ohe H, Uemoto S, Tottori J, Bando T, Date H, Koshiba T. Value of FOXP3 Expression in Peripheral Blood as Rejection Marker After Miniature Swine Lung Transplantation. J. Heart Lung Transplant. 27:1293-1301, 2008.
  • Wing, K., Onishi, Y., Prieto-Martin, P., Yamaguchi, T., Miyara, M., Fehervari, Z., Nomura, T., and Sakaguchi, S. CTLA-4 control over Foxp3+ regulatory T cell function. Science. 322:271-275, 2008.
  • Li, Y., Zhao, X., Cheng, D., Haga, H., Tsuruyama, T., Wood, K., Sakaguchi, S., Tanaka, K., Uemoto, S., and Koshiba, T. The presence of FOXP3 expressing T cells within grafts of tolerance human liver transplant recipients. Transplantation. 86:1837-1843,2008
  • Wakasa-Morimoto, C., Toyosaki-Maeda, T., Matsutani, T., Yoshida, R., Nakamura-Kikuoka, S., Maeda-Tanimura, M., Yoshitomi, H., Hirota, K., Hashimoto, H., Masaki, H., Fujii, F., Sakata, T., Tsuruta, Y., Suzuki, R., Sakaguchi, N., and Sakaguchi, S. Arthritis and pneumonitis produced by the same T-cell clones from mice with spontaneous autoimmune arthritis. Int. Immunol. 20:1331-1342, 2008.
  • Onishi, Y., Fehervari, Z., Yamaguchi, T., and Sakaguchi, S. Foxp3+ natural regulatory T cells preferentially form aggregates on dendritic cells in vitro and actively inhibit their maturation. Proc. Natl. Acad. Sci. USA. 29:10113-10118, 2008.
  • Sakaguchi, S., Yamaguchi, T., Nomura, T., and Ono, M. Regulatory T cells and immune tolerance. Cell. 133: 775-787, 2008.
  • Sakaguchi, S. Regulatory T cells in the past and for the future. Eur. J. Immunol. 38:901-937, 2008.
  • Yamaguchi T, Hirota K, Nagahama K, Ohkawa K, Takahashi T, Nomura T, Sakaguchi S. Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor. Immunity. 27:145-159, 2007.
  • Ono M, Yaguchi H, Ohkura N, Kitabayashi I, Nagamura Y, Nomura T, Miyachi Y, Tsukada T, Sakaguchi S. Foxp3 controls regulatory T cell function via interacting with AML1/Runx1. Nature. 446:685-689, 2007.
  • Hirota K, Yoshitomi H, Hashimoto M, Maeda S, Teradaira S, Sugimoto N, Yamaguchi T, Nomura T, Ito H, Nakamura T, Sakaguchi N, Sakaguchi S. Preferential recruitment of arthritogenic Th17 cells to inflamed joints via CCR6/CCL20 in rheumatoid arthritis and its animal model. J. Exp. Med. 204:2803-2812, 2007
  • Sakaguchi S, Powrie F. Emerging challenges in regulatory T cell function and biology. Science. 317:627-629, 2007.
  • Sakaguchi S, Wing K, Miyara M. Regulatory T cells in brief history and perspective. Eur. J. Immunol. 37:s116-123, 2007
  • Nomura T, Sakaguchi S. Foxp3 and Aire in thymus-generated T(reg) cells: a link in self-tolerance. Nat Immunol. 8:333-334, 2007.
  • Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol Med. 13:108-116, 2007.
  • Hirota K, Hashimoto M, Yoshitomi H, Tanaka S, Nomura T, Yamaguchi T, Iwakura Y, Sakaguchi N, Sakaguchi S. T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis. J Exp Med. 204:41-47, 2007.
  • Yamaguchi T, Sakaguchi S. Skin controls immune regulators. Nat Med. 12:1358-1359, 2006.
  • Katakai T, Nomura T, Gonda H, Sugai M, Agata Y, Nishio A, Masuda T, Sakaguchi S, Shimizu A. Spontaneous Large-Scale Lymphoid Neogenesis and Balanced Autoimmunity versus Tolerance in the Stomach of H+/K+-ATPase-Reactive TCR Transgenic Mouse. J Immunol. 177:7858-67, 2006.
  • Wing, K. and Sakaguchi, S. Regulatory T cells in allergy. Curr. Opin. Allergy and Immunol. 6:482-8, 2006.
  • Fehervari, Z. and Sakaguchi, S. Peacekeepers of the immune system. Sci Am. 295:56-63, 2006.
  • Wing, K., Fehervari, Z., and Sakaguchi, S. Emerging possibilities in the development and function of regulatory T cells. Int. Immunol. 18:991-1000, 2006.
  • Sugimoto, N., Oida, T., Hirota, K., Nakamura, K., Nomura, T., Uchiyama, T., and Sakaguchi, S. Foxp3-dependent and -independent molecules specific for CD25+CD4+ natural regulatory T cells revealed by DNA microarray analysis. Int. Immunol. 18:1197-1209, 2006.
  • Nishioka, T., Shimizu, J, Iida, R., Yamazaki, S., and Sakaguchi, S. CD4+ CD25+Foxp3+ T cells and CD4+CD25-Foxp3+ T cells in aged mice. J. Immunol. 176:6586-6593, 2006.
  • Sakaguchi, S., Ono, M., Setoguchi, R., Hori, S., Fehervari, Z., Shimizu, J., Takahashi, T., and Nomura, T. Foxp3+CD25+CD4+ natural regulatory T cells in dominant self-tolerance and autoimmune disease. Immunol. Rev. 212:8-27, 2006.
  • Ono, M., Shimizu, J., Miyachi, Y., and Sakaguchi, S. Induction of fatal autoimmune myocarditis and other autoimmune diseases in mice by depleting Foxp3-expressing naturally arising CD4+ regulatory T cells. J. Immunol. 176:4748-4756, 2006.
  • Fehervari, Z., Yamaguchi, T., and Sakaguchi, S. The dichotomous roles of IL-2: tolerance versus immunity. Trends Immunol. 27:109-111, 2006.
  • Sakaguchi, S., Sakaguchi, N., Yoshitomi, H., Hata, H., Takahashi, T., and Nomura, T. Spontaneous development of autoimmune arthritis due to genetic anomaly of T cell signal transduction: Part 1. Semin. Immunol. 18:199-206, 2006.
  • Yamaguchi, T. and Sakaguchi, S. Regulatory T cells in immune surveillance and treatment of cancer. Semin. Cancer Biol. 16:115-123, 2006.
  • Sakaguchi, S., Takahashi, T., Hata, H., Yoshtomi, H., Tanaka, S., Hirota, K., Nomura, T., and Sakaguchi, N. SKG mice, a monogenic model of autoimmune arthritis due to altered signal transduction in T cells. In The hereditary Basis of Rheumatic Diseases, Progress in Inflammation Research. Edited by RikardHolmdahl, Birkhaeuser Verlag, Basel, p147-159, 2006.
  • Sakaguchi, S., Setoguchi, R., Yagi, H., and Nomura, T. Naturallyarising Foxp3-expressing CD25+CD4+ regulatory T cells in self-tolerance and autoimmune disease. Curr Top Microbiol Immunol. 305:51-66, 2006.
  • Fehervari, Z. and Sakaguchi, S. T lymphocytes: Regulatory. Nature Encyclopedia of Life Sciences. Wiley Interscience, 2006. Available at www.els.net.
  • Sakaguchi, S., Sakaguchi, N. Animal models of arthritis caused by systemic alteration of the immune system. Curr Opin Immunol. 17: 589-594, 2005.
  • Ko, K., Yamazaki, S., Nakamura, K., Nishioka, T., Hirota, K., Yamaguchi, T., Shimizu, J., Nomura, T., Chiba, T., and Sakaguchi, S. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J. Exp. Med. 202: 885-891, 2005.
  • Nishikawa, H., Kato, T., Tawara, I., Saito, K., Ikeda, H., Kuribayashi, K., Allen, P. M., Schreiber, R. D., Sakaguchi, S., Old, L. J., Shiku, H. Definition of target antigens for naturally occurring CD4+CD25+ regulatory T cells. J. Exp. Med. 201: 681-686, 2005.
  • Sakaguchi, S., and Sakaguchi, N. History of CD25+CD4+ regulatory T cells. In Regulatory T cells in inflammation, Progress in Inflammation Research. Eds. L. S. Taams, A. N. Akbar, and M. H. M. Wauben, Birkhaeuser Verlag, Basel, p3-17, 2005.
  • Nomura, T., and Sakaguchi, S. Regulatory T cells in tumor immunity. Curr Top Microbiol Immunol. 293:287-302, 2005.
  • Sakaguchi, S. and Sakaguchi, N. Regulatory T cells in immunologic self-tolerance and autoimmune diseases. Int. Rev. Immunol. 24:211-226, 2005.
  • Fehervari Z, Sakaguchi S. CD4+ regulatory cells as a potential Immunotherapy. Philos Trans R Soc Lond B Biol Sci. 360:1647-1661, 2005.
  • Sakaguchi, S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat. Immunol. 6: 345-352, 2005.
  • Kuroda N, Mitani T, Takeda N, Ishimaru N, Arakaki R, Hayashi Y, Bando Y, Izumi K, Takahashi T, Nomura T, Sakaguchi S, Ueno T, Takahama Y, Uchida D, Sun S, Kajiura F, Mouri Y, Han H, Matsushima A, Yamada G, Matsumoto M. Development of Autoimmunity against Transcriptionally Unrepressed Target Antigen in the Thymus of Aire-Deficient Mice. J. Immunol. 174:1862-1870, 2005.
  • Setoguchi, R., Hori, S., Takahashi, T., and Sakaguchi, S. Homeostatic maintenance of natural Foxp3+ CD25+ CD4+ regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization J. Exp. Med. 201:723-735, 2005.
  • Yoshitomi, H., Sakaguchi, N., Brown, G., Tagami, T., Sakihama,T., Nomura, T., Akira, S., Gordon, S., Nakamura, T., and Sakaguchi, S. Environmental stimulation of innate immunity triggers chronic arthritis in mice genetically prone to produce arthritogenic autoimmune T cells: a key role of fungal β-glucans and their receptor Dectin-1. J. Exp. Med. 201: 949-960, 2005.
  • Fehervari, Z., and Sakaguchi, S.: Regulatory T cells. In Measuring Immunity, eds. M. T. Lotze and A. W. Thompson, Elsevier. p322-335, 2005. Fehervari, Z., and Sakaguchi, S. CD4+ regulatory T cells and immune control. J. Clin. Invest. 114:1209-117, 2004.
  • Yagi, H., Nomura, T., Nakamura, K., Kitawaki, T., Hori, S., Maeda, M., Onodera, M., Uchiyama, T., Fujii, S., and Sakaguchi, S. Crucial role of FOXP3 in the development and function of human CD25+CD4+ regulatory T cells. Int. Immunol. 16: 1643-1656, 2004.
  • Kanamaru, F., Youngnak, P., Hashiguchi, M., Nishioka, T., Takahashi, T., Sakaguchi, S., Ishikawa, I., and Azuma, M. Costimulation via glucocorticoid-induced TNF receptor in both conventional and CD25+ regulatory CD4+ T cells. J. Immunol. 172: 7306-7314, 2004.
  • Fehervari, Z., and Sakaguchi, S.: Control of CD25+CD4+ regulatory T cell activation and function by dendritic cells. Int. Immunol. 16:1769-1780, 2004.
  • Hata, H., Sakaguchi, N., Yoshitomi, H., Iwakura, Y., Sekikawa, K., Rennick, D., Azuma, Y., Kanai, C., Moriizumi, E., Nakamura, T., and Sakaguchi, S. Distinct contribution of IL-6, TNF-α, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J. Clin. Invest. 114: 582-588, 2004.
  • Nishimura, E., Sakihama, T., Setoguchi, R., Tanaka. K., and Sakaguchi, S. Induction of antigen-specific immunologic tolerance by in vivo and in vitro antigen-specific expansion of naturally arising CD25+CD4+ regulatory T cells. Int. Immunol. 16: 1189-1201, 2004.
  • Dittmer, U., He, H., Messer, R. J., Schimmer, S., Olbrich, A. R., Ohlen, C., Greenberg, P. D., Stromnes, I. M., Iwashiro, M., Sakaguchi, S., Evans, L. H., Peterson, K. E., Yang, G., Hasenkrug, K. J. Functional impairment of CD8+ T cells by regulatory T cells during persistent retroviral infection. Immunity. 20: 1-20, 2004.
  • Fehervari, Z., and Sakaguchi, S. Development and function of CD25+CD4+ regulatory T cells. Curr Opin Immunol. 16:203-208, 2004.
  • Hori, S., and Sakaguchi, S. Foxp3, a critical regulator of regulatory T cell development and function. Microbes Infect. 6: 745-51, 2004.
  • Sakaguchi, S.: Naturally arising CD4+ regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22:531-562, 2004.
  • Kajiura, F., S. Sun, T. Nomura, K. Izumi, T. Ueno, Y. Bando, N. Kuroda, H. Han, Yi Li, A. Matsushima, Y. Takahama, S. Sakaguchi, T. Mitani and M. Matsumoto. NF-kB-inducing kinase establishes self-tolerance in a thymic-stroma dependent manner. J. Immunol. 172: 2067-2075, 2004.
  • Sakaguchi, S. The origin of FOXP3-expressing CD4+ regulatory T cells: thymus or periphery. J. Clin. Invest. 112: 1310-1312, 2003.
    Sakaguchi, N., Takahashi, T., Hata, H., Nomura, T., Tagami, T., Yamazaki, S., Sakihama, T., Matsutani, T., Negishi, I., Nakatsuru, S., and Sakaguchi, S. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 426:454-60, 2003
  • Sakaguchi, S. Taming transplantation by regulatory T cells. Nat Med. 9:1117-1118, 2003.
  • Takahashi, T. and Sakaguchi, S. Naturally arising CD25+CD4+ regulatory T cells in maintaining immunologic self-tolerance and preventing autoimmune disease. Curr. Mol. Med. 3: 693-706, 2003.
  • Hori, S., Takahashi, T., and Sakaguchi, S. Control of autoimunity by natural regulatory T cells. Adv. Immunol. 81: 329-369, 2003.
  • Sakaguchi, S. Control of immune responses by naturally arising CD4+ regulatory T cells. J. Exp. Med. 197: 397-401, 2003
  • Hori, S., Nomura, T., and Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 299: 1057-1061, 2003.
  • Wood, K. and Sakaguchi, S. Regulatory T cells in transplantation. Nat. Rev. Immunol. 3: 199-210, 2003.
  • Sakaguchi, S. Regulatory T cells: mediating compromises between host and parasite. Nat Immunol. 4: 10-11, 2003.
  • Takahashi, T., and Sakaguchi, S. The role of regulatory T cells in controlling immunologic self-tolerance. Int. Rev. Cytol. 225: 1-32, 2003.
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