Lympho-epithelial interactions in the thymus for T-cell repertoire formation

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790540
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Immunology
• Research Institution: Research Institute, International Medical Center of Japan
• Principal Investigator: NITTA Takeshi 独立行政法人国立国際医療研究センター, 研究所, 室長 (30373343)
• Project Period (FY): 2011 – 2012
• Keywords: 獲得免疫 / 胸腺

Research Abstract

Distinct subsets of thymic epithelial cells support development of repertoire selection of T cells. We found that cortical thymic epithelial cells form multicellular complexes that closely associate with many viable thymocytes. The complexes that completely enclose thymocytes were found to be identical to previously described “thymic nurse cells (TNCs)”. Our results showed that the formation of TNC complexes requires pre-selected CD4^+CD8^+ thymocytes in postnatal thymus. Cells within TNC complexes were enriched for long-lived CD4^+CD8^+ thymocytes that have undergone secondary TCRα rearrangement. These results indicate that cortical thymic epithelial cells interact with pre-selected CD4^+CD8^+ thymocytes to form TNC complexes that provide a microenvironment supporting secondary TCRα rearrangement and T-cell selection.

Research Products

• [Journal Article] The development of T lymphocytes in fetal thymus organ culture. (2013)
  • Author(s): Nitta, T., Ohigashi, I., Takahama, Y.
  • Journal Title: Methods Mol Biol Volume: 946 Pages: 85-102
  • DOI: DOI:10.1007/978-1-62703-128-8_6
  • Peer Reviewed
• [Journal Article] Thymic nurse cells provide microenvironment for secondary TCRα rearrangement in cortical thymocytes. (2012)
  • Author(s): Nakagawa, Y. Ohigashi, I., Nitta, T., Sakata, M., Tanaka, K., Murata, S., Kanagawa, O., Takahama, Y
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Pages: 20572-20577
  • DOI: DOI:10.1073/pnas.1213069109
  • Peer Reviewed
• [Journal Article] MicroRNAs Control the Maintenance of Thymic Epithelia and Their Competence for T Lineage Commitment and Thymocyte Selection. (2012)
  • Author(s): Zuklys, S., Mayer, C.E., Zhanybekova, S., Stefanski, H.E., Nusspaumer, G., Gill, J., Barthlott, T., Chappaz, S., Nitta, T., Dooley, J., Nogales-Cadenas, R., Takahama, Y., Finke, D., Liston, A., Blazar, B.R., Pascual-Montano, A., Hollander, G.A.
  • Journal Title: J Immunol Volume: 189 Pages: 3894-3904
  • DOI: DOI:10.4049/jimmunol.1200783
  • Peer Reviewed
• [Journal Article] Rank Signaling Links the Development of Invariant γδ T Cell Progenitors and Aire^+ Medullary Epithelium. (2012)
  • Author(s): Roberts, N.A., White, A.J., Jenkinson, W.E., Turchinovich, G., Nakamura, K., Withers, D.R., McConnell, F.M., Desanti, G.E., Benezech, C., Parnell, S.M., Cunningham, A.F., Paolino, M., Penninger, J.M., Simon, A.K., Nitta, T., Ohigashi, I., Takahama, Y., Caamano, J.H., Hayday, A.C., Lane, P.J., Jenkinson, E.J., Anderson, G.
  • Journal Title: Immunity Volume: 36 Pages: 427-437
  • DOI: DOI:10.1016/j.immuni.2012.01.016
  • Peer Reviewed
• [Journal Article] CCR7 with S1P_1 signaling through AP-1 for migration of Foxp3^+ regulatory T-cells controls autoimmune exocrinopathy. (2012)
  • Author(s): Ishimaru, N., Yamada, A., Nitta, T., Arakaki, R., Lipp, M., Takahama, Y., Hayashi Y
  • Journal Title: Am J Pathol Volume: 180 Pages: 199-208
  • DOI: DOI:10.1016/j.ajpath.2011.09.027
  • Peer Reviewed
• [Presentation] 胸腺皮質微小環境の形成と機能 (2013)
  • Author(s): 新田 剛
  • Organizer: 第10回Osteoimmunology Forum
  • Place of Presentation: 東京
  • Year and Date: 2013-03-30
• [Presentation] T 細胞分化におけるThemis 分子内ドメインの役割 (2012)
  • Author(s): 新田 剛、岡田季之、加地健太郎、小田浩代、高島明子、Michael S. Patrick、鈴木春巳
  • Organizer: 第35回日本分子生物学会年会
  • Place of Presentation: 福岡
  • Year and Date: 2012-12-12
• [Presentation] Distinct protein motifs in Themis regulate positive selection of T cells (2012)
  • Author(s): Takeshi Nitta, Toshiyuki Okada, Hiroyo Oda, Akiko Takashima, Michael S. Patrick, Harumi Suzuki
  • Organizer: 第41回日本免疫学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-06
• [Presentation] Themis 分子内ドメインの機能解析 (2012)
  • Author(s): 新田 剛、岡田季之、加地健太郎、小田 浩代、高島明子、Michael S. Patrick、鈴木春巳
  • Organizer: 第22回 Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2012-07-06
• [Presentation] Lympho-epithelial complexes in the thymic cortex (2011)
  • Author(s): Takeshi Nitta, Izumi Ohigashi, Yasushi Nakagawa, Yousuke Takahama
  • Organizer: 第40回日本免疫学会総会・学術集会
  • Place of Presentation: Chiba, Japan
  • Year and Date: 2011-11-28
• [Presentation] 胸腺皮質上皮細胞と胸腺細胞の多細胞複合体 (2011)
  • Author(s): 新田 剛、新田幸子、中川靖士、高浜洋介
  • Organizer: 第21回 Kyoto T Cell Conference
  • Place of Presentation: 京都
  • Year and Date: 2011-06-10