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Published on: November 8, 2016
Roles of regulatory T cells in the pathogenesis of pediatric aplastic anemia
Shaofen Lin1, Lele Hou1, Su Liu1
1a Department of Paediatric Hematopathy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University , Guangzhou , Guangdong , China.
Insights
Regulatory T cells (Tregs) are decreased and functionally impaired in children with aplastic anemia (AA). This study investigated Treg changes in pediatric AA, revealing lower Treg proportions and impaired function at diagnosis.
Area of Science:
- Immunology
- Hematology
- Pediatric Medicine
Background:
- The pathogenesis of pediatric aplastic anemia (AA) remains unclear.
- Regulatory T cells (Tregs) play a crucial role in immune regulation.
- Understanding Treg dynamics in pediatric AA is essential for elucidating disease mechanisms.
Purpose of the Study:
- To investigate alterations in the proportion and function of regulatory T cells (Tregs) in pediatric aplastic anemia (AA).
- To assess the impact of immunosuppressive therapy (IST) on Treg levels in pediatric AA.
- To correlate Treg status with treatment response in pediatric AA.
Main Methods:
- Flow cytometry was used to determine Treg proportions in peripheral blood and bone marrow.
- mRNA levels of transcription factors (FOXP3, STAT3, T-BET) were quantified using RT-PCR.
- Cytokine concentrations (interferon-γ, interleukin-17, TGF-β) were measured by ELISA.
- Treg function was assessed through co-culture assays with effector T cells (Teff).
- Treg proportions were monitored dynamically following IST.
Main Results:
- Untreated pediatric AA patients exhibited significantly lower proportions of Tregs in peripheral blood and bone marrow compared to controls.
- mRNA levels of FOXP3 and STAT3 were reduced in AA patients, while T-BET levels showed no significant difference.
- Elevated levels of interferon-γ and interleukin-17, and decreased TGF-β were observed in AA patients.
- The immunosuppressive function of Tregs was impaired in pediatric AA.
- Post-IST, Treg proportions remained lower than in controls, with no significant change upon AA resolution.
Conclusions:
- Pediatric aplastic anemia is characterized by significantly decreased and functionally impaired regulatory T cells at diagnosis.
- Treg levels are diminished even after immunosuppressive therapy and do not recover upon disease resolution.
- These findings highlight the critical role of Tregs in the pathogenesis and immune dysregulation of pediatric AA.
Abstract:
The pathogenesis of aplastic anemia (AA) in children is not clear. This study was conducted to investigate the changes in the proportion and function of regulatory T cells (Tregs) in pediatric AA. The proportion of Tregs, mRNA levels of transcription factors, and concentrations of cytokines were measured by flow cytometry, reverse transcription-PCR, and enzyme-linked immunosorbent assay, respectively. Tregs were co-cultured with effector T cells (Teff) to evaluate the function of Tregs. The proportion of Tregs after immunosuppressive therapy (IST) in pediatric AA was monitored dynamically. Compared to the control, the proportions of Tregs in peripheral blood and bone marrow lymphocytes of the untreated AA group were lower (1.31% ± 0.73% vs. 3.16% ± 0.92%, 1.49% ± 0.81% vs. 3.06% ± 0.82%, respectively, p < 0.001). The mRNA levels of FOXP3 and STAT3 in the AA group were lower (p = 0.014; p < 0.001). However, the mRNA levels of T-BET did not significantly differ between groups. The concentration of interferon-γ and interleukin-17 in the AA group were higher (p = 0.004; p = 0.003), whereas the concentration of TGF-β decreased (p = 0.044). The immunosuppressive function of Tregs was impaired in the AA group. After IST, the proportion of Tregs was significantly lower than that in the control. The proportion of Tregs at the time of diagnosis in the nonresponsive group was lower than that in the responsive group, but the difference was not significant. Treg levels were significantly decreased and were functionally impaired at the time of diagnosis of pediatric AA. However, there was no significant change in Tregs at the resolution of AA.
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