Analysis of intestinal CD4-CD8- double negative T cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09301
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: OKADA Eriko 東京医科歯科大学, 大学院医歯学総合研究科, 講師 (20376784)
• Co-Investigator(Kenkyū-buntansha): 根本 泰宏 東京医科歯科大学, 大学院医歯学総合研究科, 助教 (20456213) ; 渡辺 守 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (10175127)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: Double Negative T細胞 / 粘膜免疫 / γδT細胞 / 腸管上皮間リンパ球

Outline of Final Research Achievements

There are huge amount of exogenous antigens, such as gut microbes and food antigens, in the intestine. To keep homeostasis, it has highly developed immune system, and it includes a various types of immune cells. Above all, γδT cells and CD4-CD8αβ-TCRαβ+T cells (Double Negative: DNT cells) are very unique. They are abundant in the intestine, while they are rare in the peripheral blood and other organs. We noticed DNT cells, which is still enigmatic fraction, and analyzed their morphological and immunological feature. We found that DNT cells are similar to γδT cells, while they are different from CD4+ T cells or CD8+　T cells in many aspect. DNT suppressed proliferation of Naive CD4+ T cells in vitro. With the adoptive transfer experiment, we found that γδ, DNT, CD4 and CD8+ T cells in the small intestine are different fraction and there are no plasticity among them. In the human intestine, we found substantial number of DNT cells, but their number is lower than mice.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

これまで機能が不明であったDNT細胞の形態学的、免疫学的特徴が明らかになった。本分画は腸管粘膜免疫における新規制御性T細胞分画として、今後炎症性腸疾患、食物アレルギー、大腸癌などの疾患の病態解明および新規治療法の開発に役立つ可能性がある。