Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, USA.
J Immunol. 2013 Mar 1;190(5):2178-87. doi: 10.4049/jimmunol.1201945. Epub 2013 Jan 21.
A plethora of work implicates important effects of the vitamin A derivative retinoic acid (RA) in myeloid differentiation, whereas fewer studies explore the role of RA in lymphoid cells. Most work on lymphoid cells has focused on the influence of RA on CD4 T cells. Little information about the role of RA in CD8 T cell differentiation is available, and even less on cell-intrinsic effects in the CD8 T cell. This study explores the role of RA in effector and memory differentiation in a cell-intrinsic manner in the context of vaccinia virus infection. We observed the loss of the short-lived effector cell phenotype (reduced KLRG1(+), T-bet(hi), granzyme B(hi)), accompanied by an enhanced memory precursor phenotype at the effector (increased CD127(hi), IL-2(+)) and contraction phases (increased CD127(hi), IL-2(+), eomesodermin(hi)) of the CD8 response in the absence of RA signaling. The lack of RA also increased the proportion of central memory CD8s. Collectively, these results introduce a new role for RA in CD8 T cell activation and differentiation. This new role may have significant implications for optimal vaccine design in which vitamin A supplementation is used to augment effector responses, but it may be to the detriment of the long-term central memory response.
大量研究表明维生素 A 衍生物视黄酸（RA）在髓系分化中具有重要作用，而较少的研究探索 RA 在淋巴细胞中的作用。大多数关于淋巴细胞的工作都集中在 RA 对 CD4 T 细胞的影响上。关于 RA 在 CD8 T 细胞分化中的作用的信息很少，而关于 CD8 T 细胞内在作用的信息则更少。本研究以细胞内在方式在痘苗病毒感染的背景下探索 RA 在效应器和记忆分化中的作用。我们观察到在 RA 信号缺失的情况下，短期效应细胞表型（降低 KLRG1(+)、T-bet(hi)、颗粒酶 B(hi)）丢失，同时在效应器（增加 CD127(hi)、IL-2(+)）和收缩阶段（增加 CD127(hi)、IL-2(+)、eomesodermin(hi)）中记忆前体细胞表型增强。RA 的缺乏也增加了中央记忆 CD8 的比例。总的来说，这些结果为 RA 在 CD8 T 细胞激活和分化中的新作用提供了依据。这一新作用可能对最佳疫苗设计具有重要意义，在这种设计中，维生素 A 补充剂被用于增强效应器反应，但这可能不利于长期的中央记忆反应。
