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Updated: Nov 17, 2025
Phenotypic and Functional Analysis of Activated Regulatory T Cells Isolated from Chronic Lymphocytic Choriomeningitis Virus-infected Mice
Published on: June 22, 2016
An enhanced level of LAMP-2A participates in CD4+T cell hyperactivity in patients with primary biliary cholangitis
Keshuai Sun1, Shuoyi Ma1, Siyuan Tian1
1State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, China.
Background:
Primary biliary cholangitis (PBC) is an immune-mediated chronic cholestasis, in which T cell homeostasis plays an important role. Lysosomal-associated membrane protein 2 isoform A (LAMP-2A) has been implicated in the regulation of CD4+T cell responses.
Methods:
We comprehensively evaluated the immunobiology of CD4+T cells in patients with PBC (PBC, n=42), chronic hepatitis B (CHB, n=20), and healthy control subjects (HC, n=20) by flow cytometry including activation status and LAMP-2A expression. Additionally, we investigated the activation responses of PBC-naïve CD4+T cells by stimulation in vitro and tested the changes caused by deleting the gene encoding LAMP-2A.
Results:
Firstly, we found an increased activation status of circulating CD4+T cells from PBC patients compared to the HC subjects, and PBC-naïve CD4+T cells showed enhanced responses after stimulation in vitro. Secondly, PBC-naïve CD4+T cells expressed a significantly higher level of LAMP-2A compared to the HC and CHB groups [PBC vs. HC, 1,954.74 (1,254.28-3,057.14) vs. 1,542.12 (961.18-2,277.98), P=0.03; vs. CHB, 1,153.59 (726.87-1,275.48), P=0.02], and the overreactions of PBC-naïve CD4+T cells could be reversed by interfering with LAMP-2A expression in vitro. Thirdly, the LAMP-2A expression level of PBC-naïve CD4+T cells was related to disease severity and drug response.
Conclusions:
An abnormally increased LAMP-2A expression of PBC-naïve CD4+T cells might be related to excessive activation responses. LAMP-2A could be a novel therapeutic target for the treatment of PBC by reversing excessive responses and consequently reducing biliary injury.
