美国弗雷德哈钦森癌症中心Geoffrey R. Hill和Albert C. Yeh共同合作，近期取得重要工作进展。他们研究提出，微生物群决定T细胞克隆选择以增强干细胞移植后的移植物抗宿主病能力。相关研究成果2024年6月13日在线发表于《免疫》杂志上。

据介绍，同种异体的T细胞扩增是移植物抗宿主病（GVHD）的主要决定因素，目前的理论认为这是由供体和受体之间的组织相容性抗原差异驱动的。这一范例代表了一个封闭的遗传系统，在该系统中，供体T细胞与肽-主要组织相容性复合体（MHC）相互作用，尽管由于T细胞库的稀疏性，克隆鉴定仍然具有挑战性。

研究人员使用小鼠干细胞移植系统中的供体和受体T细胞受体（TCR）频率开发了一个贝叶斯模型，以定义遗传上相同的供体-受体对中T细胞克隆的有限共同扩增。供体CD4⁺ T细胞克隆型的一个子集在相同的受体中差异扩增，并且是微生物群依赖性的。微生物群特异性T细胞增强了GVHD的致死性，并可以靶向胃肠道上皮在同种异体反应过程中呈递的微生物抗原。

总之，微生物群是同源抗原的来源，有助于克隆型T细胞的扩增和GVHD的诱导，与供体-受体遗传学无关。

附：英文原文

Title: Microbiota dictate T cell clonal selection to augment graft-versus-host disease after stem cell transplantation

Author: Albert C. Yeh, Motoko Koyama, Olivia G. Waltner, Simone A. Minnie, Julie R. Boiko, Tamer B. Shabaneh, Shuichiro Takahashi, Ping Zhang, Kathleen S. Ensbey, Christine R. Schmidt, Samuel R.W. Legg, Tomoko Sekiguchi, Ethan Nelson, Shruti S. Bhise, Andrew R. Stevens, Tracy Goodpaster, Saranya Chakka, Scott N. Furlan, Kate A. Markey, Marie E. Bleakley, Charles O. Elson, Philip H. Bradley, Geoffrey R. Hill

Issue&Volume: 2024-06-13

Abstract: Allogeneic T cell expansion is the primary determinant of graft-versus-host disease(GVHD), and current dogma dictates that this is driven by histocompatibility antigendisparities between donor and recipient. This paradigm represents a closed geneticsystem within which donor T cells interact with peptide-major histocompatibility complexes(MHCs), though clonal interrogation remains challenging due to the sparseness of theT cell repertoire. We developed a Bayesian model using donor and recipient T cellreceptor (TCR) frequencies in murine stem cell transplant systems to define limitedcommon expansion of T cell clones across genetically identical donor-recipient pairs.A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiotadependent. Microbiota-specific T cells augmented GVHD lethality and could target microbialantigens presented by gastrointestinal epithelium during an alloreactive response.The microbiota serves as a source of cognate antigens that contribute to clonotypicT cell expansion and the induction of GVHD independent of donor-recipient genetics.

DOI: 10.1016/j.immuni.2024.05.018

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00273-5