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Updated: Oct 15, 2025
Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
Increased Expression of CD95 in CD4+ Effector Memory T Cells Promotes Th17 Response in Patients with Myasthenia
Xiaoyu Huang1, Jie Zhu1,2, Tan Liu1,3
1Department of Neurology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Insights
Increased CD95 expression on CD4+ effector memory T cells in myasthenia gravis (MG) patients promotes Th17 responses. This finding suggests CD95 as a potential therapeutic target for managing MG severity.
Area of Science:
- Immunology
- Autoimmune Disorders
- T cell biology
Background:
- CD95 (also known as Fas) signaling can promote inflammation beyond apoptosis.
- Autoimmune disorders like myasthenia gravis (MG) involve complex immune dysregulation.
Purpose of the Study:
- To investigate the role of CD95 expression in CD4+ effector memory T (CD4+ TEM) cells in myasthenia gravis (MG).
- To explore the relationship between CD95 expression, disease severity, and Th17 cell responses in MG patients.
Main Methods:
- Quantification of CD95 expression on CD4+ TEM cells in MG patients.
- Correlation analysis of CD95 levels with clinical scores (QMGs), IL-17 levels, and plasma cell frequencies.
- In vitro studies using anti-CD95 monoclonal antibody (mAb) and siRNA to assess effects on Th17 differentiation.
- Investigation of signaling pathways (p38, Erk1/2 MAPK) involved in CD95-mediated Th17 responses.
Main Results:
- CD95 expression was elevated in CD4+ TEM cells of MG patients and correlated with disease severity.
- Glucocorticoid treatment reduced CD95 expression and associated inflammatory markers.
- In vitro, CD95 stimulation promoted Th17 cell development via p38 and Erk1/2 MAPK pathways, independent of their direct role in CD95-induced increases.
- Increased CD95 expression on CD4+ TEM cells drives Th17 responses in the MG microenvironment.
Conclusions:
- Elevated CD95 expression on CD4+ TEM cells is a key feature of myasthenia gravis.
- CD95 signaling contributes to the pro-inflammatory Th17 environment in MG.
- Targeting CD95 may offer a novel therapeutic strategy for myasthenia gravis.
Abstract:
Emerging data have revealed that CD95 can evoke non-apoptotic signals, thereby promoting pro-inflammatory functions that link to the severity of autoimmune disorders. Here, we reported that the expression of CD95 in CD4+ effector memory T (CD4+ TEM) cells was increased in myasthenia gravis (MG) patients. We also found increased expression of CD95 in CD4+ TEM cells from MG patients correlated positively with clinical severity scores (QMGs), serum IL-17 levels and plasma cells (PCs) frequencies. Conventional treatment, such as glucocorticoid, could down-regulate the expression of CD95 in CD4+ TEM cells, QMGs, serum IL-17 levels and PCs frequencies from MG patients. In vitro, low-dose of agonistic anti-CD95 mAb could promote Th17 cell development. This effect was reversed by CD95 siRNA. Moverover, CD95 stimulation induced the phosphorylation of p38 and Erk1/2 and Th17 cell differentiation, and p38 specific inhibitor SB203580 or Erk1/2 specific inhibitor PD98059 could induce opposite changes. However, SB203580 or PD98059 do not abrogate the increase of CCR6+IL-17A+ cells, ROR-γt and IL-17 expression induced by CD95 triggering relatively to each corresponding control. This suggests that p38 and Erk1/2 MAPK pathway plays a role in expression of CCR6+IL-17A+ cells, ROR-γt and IL-17, but not in their increase induced by CD95 triggering. Taken together, this study revealed that increased expression of CD95 in CD4+ TEM cells promotes Th17 response under the microenvironment of MG.
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