Whitmire Jason K, Eam Boreth, Whitton J Lindsay
Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
Eur J Immunol. 2009 Jun;39(6):1494-504. doi: 10.1002/eji.200838959.
Stem cell antigen-1 (Sca1, Ly-6A/E) is a well-established marker of murine hematopoietic stem cells, and also is expressed on memory T cells. It has been suggested that the functional maintenance of T-cell memory requires the expression of Sca1 on a specialized population of memory T cells termed "memory stem cells". Here, we evaluate the requirement for Sca1 in the primary T-cell response to virus infection, and in the establishment and maintenance of T-cell memory. We find that Sca1 expression increases on almost all CD4(+) and CD8(+) T cells during virus infection, and remains high on virus-specific memory cells. However, Sca1-deficient (Sca1KO) mice generate normal primary T-cell responses to infection; the kinetics, the immunodominance hierarchy, and the absolute numbers of CD4(+) and CD8(+) T cells are essentially indistinguishable from those observed in WT mice. Furthermore, by several criteria, primary and memory T cells in Sca1-deficient mice are phenotypically and functionally normal. These data indicate that Sca1, although perhaps a useful marker of virus-specific memory T cells, is not required for the regulation of T-cell quantity or quality, or for the development of a competent pool of memory cells.
干细胞抗原-1(Sca1,Ly-6A/E)是一种公认的小鼠造血干细胞标志物,在记忆性T细胞上也有表达。有人提出,T细胞记忆的功能维持需要在一类称为“记忆干细胞”的特殊记忆性T细胞群体上表达Sca1。在此,我们评估了Sca1在病毒感染引发的初始T细胞应答以及T细胞记忆的建立和维持过程中的必要性。我们发现,在病毒感染期间,几乎所有CD4(+)和CD8(+) T细胞上的Sca1表达均增加,并且在病毒特异性记忆细胞上仍维持高水平。然而,Sca1基因敲除(Sca1KO)小鼠对感染产生正常的初始T细胞应答;CD4(+)和CD8(+) T细胞的动力学、免疫显性等级以及绝对数量与野生型(WT)小鼠中观察到的情况基本无差异。此外,根据多项标准,Sca1基因敲除小鼠中的初始T细胞和记忆性T细胞在表型和功能上均正常。这些数据表明,Sca1虽然可能是病毒特异性记忆性T细胞的一个有用标志物,但在调节T细胞数量或质量以及发育有功能的记忆细胞库方面并非必需。