Department of Microbiology and Immunology, University of British Columbia, Vancouver, BC, Canada.
Department of Pediatrics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.
Eur J Immunol. 2018 May;48(5):803-814. doi: 10.1002/eji.201747263. Epub 2018 Jan 19.
Expansion and death of effector CD8 T cells are regulated to limit immunopathology and cells that escape contraction go on to generate immunological memory. CD44, a receptor for the extracellular matrix component hyaluronan, is a marker of activated and memory T cells. Here, we show with a murine model that the increase in CD44 expression and hyaluronan binding induced upon CD8 T cell activation was proportional to the strength of TCR engagement, thereby identifying the most strongly activated T cells. When CD44 and CD44 OT-I CD8 T cells were adoptively transferred into mice challenged with Listeria-OVA, there was a slight increase in the percentage of CD44 cells at the effector site. However, CD44 cells were out-competed by CD44 cells after the contraction phase in the lymphoid tissues, and the CD44 cells preferentially formed more memory cells. The hyaluronan-binding CD44 CD8 effector T cells showed increased pAkt expression, higher glucose uptake, and were more susceptible to cell death during the contraction phase compared to non-binding CD44 and CD44 OT-I CD8 T cells, suggesting that CD44 and its engagement with hyaluronan skews CD8 T cells toward a terminal effector differentiation state that reduces their ability to form memory cells.
效应 CD8 T 细胞的扩增和死亡受到调控，以限制免疫病理。逃脱收缩的细胞继续产生免疫记忆。细胞表面 CD44 是细胞外基质成分透明质酸的受体，是激活和记忆 T 细胞的标志物。在这里，我们通过一个鼠模型表明，CD8 T 细胞激活后 CD44 表达和透明质酸结合的增加与 TCR 结合的强度成正比，从而鉴定出最强激活的 T 细胞。当 CD44 和 CD44 OT-I CD8 T 细胞被过继转移到感染李斯特菌-OVA 的小鼠中时，效应部位的 CD44 细胞百分比略有增加。然而，在淋巴组织的收缩阶段，CD44 细胞被 CD44 细胞所取代，并且 CD44 细胞优先形成更多的记忆细胞。与非结合型 CD44 和 CD44 OT-I CD8 T 细胞相比，结合透明质酸的 CD44 CD8 效应 T 细胞表现出更高的 pAkt 表达、更高的葡萄糖摄取率，并且在收缩阶段更容易发生细胞死亡，这表明 CD44 及其与透明质酸的结合使 CD8 T 细胞向终末效应分化状态倾斜，从而降低了其形成记忆细胞的能力。
