The Clinical Significance of Hepatic CD69+CD103+CD8+ Resident-Memory T Cells in Autoimmune Hepatitis

作者：You, Zhengrui; Li, You; Wang, Qixia; Zhao, Zhibin; Li, Yikang; Qian, Qiwei; Li, Bo; Zhang, Jun; Huang, Bingyuan; Liang, Jubo; Chen, Ruiling; Lyu, Zhuwan; Chen, Yong; Lian, Min; Xiao, Xiao; Miao, Qi; Fang, Jingyuan; Lian, Zhexiong; Gershwin, M. Eric^*; Tang, Ruqi^*; Ma, Xiong^*

来源：Hepatology, 2021, 74(2): 847-863.

DOI：10.1002/hep.31739

• LIVER
• MANAGEMENT
• UNIVERSAL
• DIAGNOSIS
• RESPONSES
• PROGRAMS
• FORM

BACKGROUND AND AIMS: The diverse inflammatory response found in the liver of patients with autoimmune hepatitis (AIH) is well established, but identification of potentially pathogenic subpopulations has proven enigmatic. @@@ APPROACH AND RESULTS: We report herein that CD69(+)CD103(+)CD8(+) tissue-resident memory T cells (T-RM) are significantly increased in the liver of patients with AIH compared to chronic hepatitis B, NAFLD, and healthy control tissues. In addition, there was a significant statistical correlation between elevation of CD8(+) T-RM cells and AIH disease severity. Indeed, in patients with successful responses to immunosuppression, the frequencies of such hepatic CD8(+) T-RM cells decreased significantly. CD69(+)CD8(+) and CD69(+)CD103(+)CD8(+) T cells, also known as CD8(+) T-RM cells, reflect tissue residency and are well known to provide intense immune antigenic responses. Hence, it was particularly interesting that patients with AIH also manifest an elevated expression of IL-15 and TGF-beta on inflammatory cells, and extensive hepatic expression of E-cadherin; these factors likely contribute to the development and localization of CD8(+) T-RM cells. Based on these data and, in particular, the relationships between disease severity and CD8(+) T(RM )cells, we studied the mechanisms involved with glucocorticoid (GC) modulation of CD8(+) T-RM cell expansion. Our data reflect that GCs in vitro inhibit the expansion of CD8(+) T-RM cells induced by IL-15 and TGF-beta and with direct down-regulation of the nudear factor Blimpl of CD8(+) T-RM cells. @@@ CONCLUSIONS: Our data suggest that CD8(+) T-RM cells play a critical role in the pathogenesis of AIH, and GCs attenuate hepatic inflammation through direct inhibition of CD8(+) T(RM)( )cell expansion.

• 单位
  上海交通大学