Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
J Immunol. 2021 May 1;206(9):2109-2121. doi: 10.4049/jimmunol.2001028. Epub 2021 Apr 15.
Ag-inexperienced memory-like T (AIMT) cells are functionally unique T cells, representing one of the two largest subsets of murine CD8 T cells. However, differences between laboratory inbred strains, insufficient data from germ-free mice, a complete lack of data from feral mice, and an unclear relationship between AIMT cells formation during aging represent major barriers for better understanding of their biology. We performed a thorough characterization of AIMT cells from mice of different genetic background, age, and hygienic status by flow cytometry and multiomics approaches, including analyses of gene expression, TCR repertoire, and microbial colonization. Our data showed that AIMT cells are steadily present in mice, independent of their genetic background and hygienic status. Despite differences in their gene expression profiles, young and aged AIMT cells originate from identical clones. We identified that CD122 discriminates two major subsets of AIMT cells in a strain-independent manner. Whereas thymic CD122 AIMT cells (innate memory) prevail only in young animals with high thymic IL-4 production, peripheral CD122 AIMT cells (virtual memory) dominate in aged mice. Cohousing with feral mice changed the bacterial colonization of laboratory strains but had only minimal effects on the CD8 T cell compartment, including AIMT cells.
Ag-经验记忆样 T (AIMT) 细胞是功能独特的 T 细胞，代表了两种最大的小鼠 CD8 T 细胞亚群之一。然而，实验室近交系之间的差异、无菌小鼠的数据不足、野生小鼠的数据完全缺乏以及衰老过程中 AIMT 细胞形成之间的关系不明确，这些都是更好地理解其生物学特性的主要障碍。我们通过流式细胞术和多组学方法（包括基因表达分析、TCR 库分析和微生物定植分析）对来自不同遗传背景、年龄和卫生状况的小鼠的 AIMT 细胞进行了全面表征。我们的数据表明，AIMT 细胞在小鼠中稳定存在，与它们的遗传背景和卫生状况无关。尽管它们的基因表达谱存在差异，但年轻和衰老的 AIMT 细胞源自相同的克隆。我们发现 CD122 以不依赖于品系的方式区分 AIMT 细胞的两个主要亚群。而胸腺 CD122 AIMT 细胞（固有记忆）仅在高胸腺 IL-4 产生的年轻动物中占主导地位，外周 CD122 AIMT 细胞（虚拟记忆）则在老年小鼠中占主导地位。与野生小鼠共同饲养改变了实验室品系的细菌定植，但对 CD8 T 细胞区室，包括 AIMT 细胞，只有最小的影响。
