組織駐留型CD8+記憶T細胞塑造次級T細胞反應
作者：
小柯機器人發布時間：2020/7/16 15:09:11
荷蘭阿姆斯特丹大學的Klaas P. J. M. van Gisbergen研究團隊的最新工作表明，組織駐留型CD8+記憶T細胞（TRM細胞）塑造局部和全身性次級T細胞反應。2020年7月13日，《自然—免疫學》雜誌在線發表了這項成果。
研究人員開發了一個獨特的譜系示蹤小鼠模型，該模型利用了T細胞中TRM定義的轉錄因子同源物Blimp-1（Hobit）來確定次級反應中TRM後代的命運。再感染後，循環中相當一部分次級記憶T細胞在TRM細胞的下遊發育。這些經歷過組織的前TRM細胞與效應記憶T細胞群體具有表型特性，但在轉錄和功能上不同於其他次級效應記憶T細胞。
TRM細胞的過繼轉移實驗證實了它們在重激活反應期間形成循環效應細胞和記憶細胞的潛力。此外，原代TRM細胞群體的特異性敲除損害了局部和系統性的繼發性T細胞應答。因此，TRM細胞在重新感染後仍保持發育可塑性，並塑造局部和全身性T細胞反應。
據介紹，TRM細胞在防止入侵病原體方面起著至關重要的作用，但尚不清楚再感染對其組織範圍的影響以及對重激活反應的貢獻。
附：英文原文
Title: Tissue-resident memory CD8 + T cells shape local and systemic secondary T cell responses
Author: Felix M. Behr, Loreto Parga-Vidal, Natasja A. M. Kragten, Teunis J. P. van Dam, Thomas H. Wesselink, Brian S. Sheridan, Ramon Arens, Rene A. W. van Lier, Regina Stark, Klaas P. J. M. van Gisbergen
Issue&Volume: 2020-07-13
Abstract: Tissue-resident memory CD8+ T cells (TRM cells) are crucial in protecting against reinvading pathogens, but the impact of reinfection on their tissue confinement and contribution to recall responses is unclear. We developed a unique lineage tracer mouse model exploiting the TRM-defining transcription factor homolog of Blimp-1 in T cells (Hobit) to fate map the TRM progeny in secondary responses. After reinfection, a sizeable fraction of secondary memory T cells in the circulation developed downstream of TRM cells. These tissue-experienced ex-TRM cells shared phenotypic properties with the effector memory T cell population but were transcriptionally and functionally distinct from other secondary effector memory T cell cells. Adoptive transfer experiments of TRM cells corroborated their potential to form circulating effector and memory cells during recall responses. Moreover, specific ablation of primary TRM cell populations substantially impaired the secondary T cell response, both locally and systemically. Thus, TRM cells retain developmental plasticity and shape both local and systemic T cell responses on reinfection. Van Gisbergen and colleagues show that tissue-resident memory T cells, genetically marked in Hobit reporter mice, can exit tissues upon reinfection and contribute to systemic memory responses.
DOI: 10.1038/s41590-020-0723-4
Source: https://www.nature.com/articles/s41590-020-0723-4