2021 Fiscal Year Final Research Report
Study of functional characteristics of cytotoxic Tfh cells and their pathological significance
Project/Area Number |
18H02632
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 49020:Human pathology-related
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Research Institution | Sapporo Medical University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2022-03-31
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Keywords | 濾胞ヘルパーT細胞 / 記憶B細胞 / DP-Tfh細胞 / 細胞傷害性Tfh細胞 / IgG4関連疾患 / 異所性リンパ組織 / Eomes / CD70 |
Outline of Final Research Achievements |
This study aimed to characterize the functional features of T follicular helper cells (Tfh cells) in ectopic lymphoid tissues with chronic inflammation. The analysis of fibroinflammatory lesions of IgG4-related disease (IgG4-RD) revealed that the Tfh cell population contained double-positive Tfh cells (DP-Tfh cells), which expressed both CD4 and CD8 and presented cytotoxicity-related molecules, including Eomes, granzymes, perforin, CRTAM, and GPR56. Studies of clinical parameters and co-culture experiments using autologous T and B cells suggest that DP-Tfh cells would regulate memory B cells. Further in vitro experiments showed that normal Tfh cells could differentiate into DP-Tfh cells under the stimulation with IL-2 and IL-7, which was highly expressed in the tissue lesions of IgG4-RD. Taken together, DP-Tfh cells may play a possible role in inhibiting memory B cell function to control the antibody production program within a persistent inflammatory environment.
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Free Research Field |
病理学、免疫学
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Academic Significance and Societal Importance of the Research Achievements |
Tfh細胞はリンパ濾胞胚中心の形成を調節し、抗原特異的な抗体の産生と液性免疫記憶の成立に関わるヘルパーT細胞である。臨床検体を用いた本研究から、異所性リンパ濾胞の形成を伴う3次免疫リンパ組織において細胞傷害活性を有するDP-Tfh細胞が多く検出され、B細胞による免疫記憶を調節する新たなメカニズムが示された。本研究は慢性炎症病態のさらなる理解につながり、また重症ウイルス感染症では細胞傷害性Tfh細胞が高頻度に認められるため、免疫関連疾患の病態背景のみならず、感染防御機構の研究においても意義ある成果と考えられる。
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