人类LY9调控CD4 T细胞对……的γ干扰素免疫。 （原文此处to后内容缺失）
Human LY9 governs CD4 T cell IFN-γ immunity to .
作者信息
Ogishi Masato, Puchan Julia, Yang Rui, Arias Andrés Augusto, Han Ji Eun, Nguyen Tina, Gutiérrez-Cózar Rebeca, Conil Clément, Seeleuthner Yoann, Rinchai Darawan, Zhang Peng, Ponsin Khoren, Chaldebas Matthieu, Feng Yi, Neehus Anna-Lena, Delmonte Ottavia M, Khan Taushif, Landegren Nils, Eriksson Daniel, Bohlen Jonathan, Peel Jessica N, Fagniez Iris, Pelham Simon J, Lei Wei-Te, Chrabieh Maya, Laine Candice, Ouair Hind, Benhsaien Ibtihal, Abid Ahmed, Abderrhamani Ghorfi Ismail, Souhi Hicham, Ouazzani Hanane, Aniss Rafik, Riminton D Sean, Kämpe Olle, Turvey Stuart E, Marr Nico, Notarangelo Luigi D, Hatipoglu Nevin, Bousfiha Aziz, Ozcelik Tayfun, El Baghdadi Jamila, Cobat Aurelie, Ma Cindy S, Abel Laurent, Puel Anne, Bustamante Jacinta, Engel Pablo, Gros Philippe, Tangye Stuart G, Sallusto Federica, Boisson-Dupuis Stéphanie, Casanova Jean-Laurent
机构信息
St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.
David Rockefeller Graduate Program, Rockefeller University, New York, NY, USA.
出版信息
Sci Immunol. 2025 May 30;10(107):eads7377. doi: 10.1126/sciimmunol.ads7377.
CD4 T cells are indispensable for optimal immunity to (), a pathogen that triggers tuberculosis (TB) in humans. -specific human CD4 T cells are known to polarize toward an interferon-γ (IFN-γ)-producing, CCR4CCR6CXCR3T-betRORγT T helper 1* cell (T1cell) memory phenotype. We report that autosomal recessive deficiency of the human lymphocytic surface receptor LY9 (SLAMF3 and CD229), which is found in less than 10 individuals in the general population, underlies TB in three unrelated patients due to selective impairment in IFN-γ production by T1 cells. T1* cells express higher levels of LY9 than other CD4 T cells. Mechanistically, LY9 polarizes naïve CD4 T cells toward memory T1* cells by inducing T-bet via signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) and RORγT (thymus-specific retinoid-related orphan receptor γ) without SAP. LY9 costimulation enhances TCR-driven IFN-γ production of memory T1*, but not T1, cells in a T cell-intrinsic manner via NFAT1 (nuclear factor of activated T cells 1) and RORγT. LY9 is likely to govern an optimal T1* cell- and IFN-γ-dependent protective immunity to in humans.
CD4 T细胞对于人类抵抗引发结核病（TB）的病原体——（此处原文缺失病原体名称）的最佳免疫反应不可或缺。已知针对该病原体的人类CD4 T细胞会极化形成产生干扰素-γ（IFN-γ）的、CCR4CCR6CXCR3T-betRORγT辅助性T1细胞（T1细胞）记忆表型。我们报告称，人类淋巴细胞表面受体LY9（信号淋巴细胞激活分子家族3和CD229）的常染色体隐性缺陷在普通人群中少于10人携带，在三名无亲缘关系的患者中是结核病的病因，这是由于T1细胞产生IFN-γ的能力受到选择性损害。T1细胞比其他CD4 T细胞表达更高水平的LY9。从机制上讲，LY9通过信号淋巴细胞激活分子（SLAM）相关蛋白（SAP）诱导T-bet以及不通过SAP诱导RORγT（胸腺特异性类视黄醇相关孤儿受体γ），将初始CD4 T细胞极化为记忆T1细胞。LY9共刺激以T细胞内在方式通过活化T细胞核因子1（NFAT1）和RORγT增强记忆T1细胞而非T1细胞的TCR驱动的IFN-γ产生。LY9可能在人类中对该病原体起着最佳的T1*细胞和IFN-γ依赖性保护性免疫的调控作用。
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