Institute of Medical Immunology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Eur J Immunol. 2014 Dec;44(12):3532-42. doi: 10.1002/eji.201344180. Epub 2014 Oct 27.
Even today it is still not completely understood how CD8(+) T-cell memory is maintained long term. Since bone marrow (BM) is a niche for immunological memory, we sought to identify long-lasting early memory CD8(+) T cells in this compartment. To achieve this, we looked for CD8(+) T cells that are able to efflux Rhodamine 123, a typical property of stem cells. Indeed, we identified a distinct subset of CD8(+) T cells in BM, with the capacity to efflux and high CD127 expression. These CD127(hi) effluxers are conventional CD8(+) T cells exhibiting a broad TCR-Vβ repertoire and are generated in response to viral peptides in vitro. CD127(hi) effluxer CD8(+) T cells have an early memory phenotype defined by preferential TNF-α production and a Bcl-2(hi) , KLRG-1(low) profile. This population has long telomeres and shows constitutively low frequencies of Ki-67 expression ex vivo, but has a high proliferative and differentiation capacity in vitro. However, IL-15 downmodulates CD127 in CD127(hi) effluxer CD8(+) T cells in vitro. Consequently, the CD127(low) effluxer subset may comprise cells recently exposed to IL-15. Taken together, CD127(hi) effluxer CD8(+) T cells represent a novel population of early memory T cells resident in BM with properties required for long-lived memory.
即使在今天,人们仍然不完全了解 CD8(+) T 细胞记忆是如何长期维持的。由于骨髓 (BM) 是免疫记忆的一个龛位,我们试图在这个部位识别持久的早期记忆 CD8(+) T 细胞。为了实现这一目标,我们寻找能够排出 Rhodamine 123 的 CD8(+) T 细胞,这是干细胞的典型特性。事实上,我们在 BM 中鉴定出了一种独特的 CD8(+) T 细胞亚群,具有排出和高 CD127 表达的能力。这些 CD127(hi) 排出细胞是具有广泛 TCR-Vβ 库的常规 CD8(+) T 细胞,是体外对病毒肽产生反应而产生的。CD127(hi) 排出细胞 CD8(+) T 细胞具有早期记忆表型,其特征是优先产生 TNF-α,以及 Bcl-2(hi)、KLRG-1(low) 特征。该群体具有长端粒,并且在体外表现出持续低频率的 Ki-67 表达,但具有高增殖和分化能力。然而,IL-15 在体外下调 CD127(hi) 排出细胞 CD8(+) T 细胞中的 CD127。因此,CD127(low) 排出细胞亚群可能包含最近暴露于 IL-15 的细胞。总之,CD127(hi) 排出细胞 CD8(+) T 细胞代表一种新型的早期记忆 T 细胞群体,存在于 BM 中,具有长期记忆所需的特性。