Disturbance in the reconstitution of distinct T-cell subsets and the incidence of GvHD following allo-HSCT in pediatric patients with non-malignant hematological disorders,Immunology Letters

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Disturbance in the reconstitution of distinct T-cell subsets and the incidence of GvHD following allo-HSCT in pediatric patients with non-malignant hematological disorders
Immunology Letters ( IF 4.4 ) Pub Date : 2023-07-18 , DOI: 10.1016/j.imlet.2023.07.008
Shideh Namazi Bayegi ₁ , Amir Ali Hamidieh ₂ , Maryam Behfar ₂ , Mahmood Bozorgmehr ₃ , Amene Saghazadeh ₄ , Nader Tajik ₅ , Ali-Akbar Delbandi ₅ , Farzaneh Tofighi Zavareh ₆ , Samaneh Delavari ₇ , Mehdi Shekarabi ₈ , Nima Rezaei ₉

Affiliation

Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Systematic Review and Meta-analysis Expert Group (SRMEG), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran.
Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran.
Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Network of Immunity in Infection, Malignancy, and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Background

The reconstitution of different T-cell subsets following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is critical for efficient pathogen protection and the prevention of graft-versus-host disease (GvHD). In particular, studies have highlighted the importance of balanced ratios of regulatory T-cells (Tregs) and distinct functionally T-cells in preventing acute and chronic GvHD.

Methods

We evaluated the regeneration of CD4 and CD8 T-cell subpopulations in nine pediatric patients with non-malignant disorders following allo-HSCT from a fully HLA-identical donor.

Results

CD4 and CD8 T-cells were higher 12 months after the transplant but still lower than in healthy controls and pre-transplant. However, we found after allo-HSCT, central memory and effector memory cell subsets were the predominant phenotypes in the CD4 and CD8 T-cell populations, respectively. In patients who had developed acute GvHD, there was an increase in the frequency of TEMRA (effector memory T cells that re-express CD45RA) cells within the CD4 T-cell population. Meanwhile, in patients with chronic GvHD, we observed a decrease in Th1 cells in CD4 T-cells and effector memory cells within the CD8 T-cell population. In addition, we found decreased TEMRA cell subsets in CD4 and CD8 T-cell populations in chronic GvHD.

Conclusion

Our findings suggest a possible relationship between the influence of acute GvHD and its prevention on delayed CD4 T-cell reconstitution and, reciprocally, unbalanced regeneration of CD4 and CD8 T-cell subsets in the development of chronic GvHD.

中文翻译：

非恶性血液病儿科患者异基因造血干细胞移植后不同 T 细胞亚群重建的紊乱和 GvHD 的发生率

背景

异基因造血干细胞移植 (allo-HSCT) 后不同 T 细胞亚群的重建对于有效的病原体保护和预防移植物抗宿主病 (G v HD) 至关重要。特别是，研究强调了调节性 T 细胞 (Treg) 和不同功能 T 细胞的平衡比例对于预防急性和慢性 G v HD的重要性。

方法

我们评估了 9 名患有非恶性疾病的儿科患者在接受来自完全 HLA 完全相同的供体的同种异体造血干细胞移植后 CD4 和 CD8 T 细胞亚群的再生情况。

结果

移植后 12 个月，CD4 和 CD8 T 细胞较高，但仍低于健康对照和移植前。然而，我们发现异基因造血干细胞移植后，中央记忆和效应记忆细胞亚群分别是CD4和CD8 T细胞群中的主要表型。在患有急性 G v HD 的患者中，CD4 T 细胞群中 TEMRA（重新表达 CD45RA 的效应记忆 T 细胞）细胞的频率增加。与此同时，在慢性 G v HD 患者中，我们观察到 CD4 T 细胞中的 Th1 细胞和 CD8 T 细胞群中的效应记忆细胞减少。此外，我们发现慢性 G v HD 中 CD4 和 CD8 T 细胞群中的 TEMRA 细胞亚群减少。