Details

Autor(en) / Beteiligte

• Li, Weiping
• Bai, Ziran
• Liu, Jiaqing
• Tang, Yawei
• Yin, Chunlai
• Jin, Minli
• Mu, Lijun
• Li, Xia

Titel

Mitochondrial ROS-dependent CD4+PD-1+T cells are pathological expansion in patients with primary immune thrombocytopenia

Ist Teil von

• International immunopharmacology, 2023-09, Vol.122, p.110597-110597, Article 110597

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •CD4+PD-1+T cells were potentially involved in ITP immunopathogenesis.•CD4+PD-1+T cells were not exhausted and retained cytokine-producing potential and positively correlated with the plasmablasts in ITP.•Increased mtROS was related to CD4+PD-1+T cell function. Aberrant-activated T cells, especially CD4+T cells, play a crucial part in the pathogenetic progress of immune thrombocytopenia (ITP). PD-1-mediated signals play a negative part in the activation of CD4+T cells. However, knowledge is limited on the pathogenic characteristics and function of CD4+PD-1+T cells in ITP. The frequency and phenotype including cell activation, apoptosis, and cytokine production of CD4+PD-1+T cells were evaluated by flow cytometry. PD-1 Ligation Assay was performed to assess the function of PD-1 pathway in CD4+T cells. Mitochondrial reactive oxygen species (mtROS) were detected by MitoSOX Red probe. Compared with healthy controls (HC), the frequencies of CD4+PD-1+T cells were significantly increased in ITP patients. However, these cells are not exhausted despite PD-1 expression. Besides retaining cytokine-producing potential, these CD4+PD-1+T cells also had a possible B-cell helper function including expressing ICOS, CD84, and CD40L. Moreover, the CD4+PD-1+T cell subset contained higher levels of mitochondrial ROS than CD4+PD-1-T cell subset in patients with ITP. And mtROS inhibition could reduce the secretion of the inflammatory cytokines and regulate the function of CD4+PD-1+T cells. Upon in-vitro T cell receptor (TCR) stimulation of CD4+T cells in the presence of plate-bound PD-L1 fusion protein (PD-L1-Ig), CD4+T cells from ITP patients appeared resistant to such PD-1-mediated inhibition of interferon (IFN)-γ secretion. The CD4+PD-1+T cells were more abundant in patients with ITP. Additionally, this CD4+PD-1+T cell subset may be a potential etiology of ITP and a potential immune therapeutic target for ITP patients in the future.