Global T-cell functionality evaluated by whole blood interferon-gamma release assay as a valuable indicator for immune reconstitution monitoring in pediatric allo-HSCT

Abstract

Background: Adequate T-cell immune reconstitution (IR) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is pivotal for the recovery and optimal outcomes of pediatric HSCT recipients. A thorough assessment of global T-cell functionality is a crucial component in monitoring T-cell IR during the post-transplant period. The purpose of this study is to provide a novel tool and strategy for assessing and monitoring T-cell IR after pediatric allo-HSCT.

Methods: This study enrolled 126 pediatric patients receiving allo-HSCT at a single institution. A standardized whole blood interferon-gamma release assay (WB-IGRA) was introduced to evaluate global T-cell functionality in different periods after HSCT.

Results: The study revealed that T-cell functionality, assessed via the WB-IGRA assay, progressively enhanced over the post-transplant period, effectively distinguishing between patients with and without immunosuppression, thereby highlighting the assay's viability in assessment of T-cell IR in children after allo-HSCT. Further analysis stratified by age revealed a more significant enhancement in T-cell functionality among children >10 years old compared to those ≤10. Conversely, when evaluating immune cell subsets, increases in CD3⁺, CD4⁺, and CD8⁺ subsets well reflected immune reconstructive progress in children ≤10 years old, whereas only increases in CD4⁺ cell subsets exhibited statistical significance in older children. Additionally, all three T cell subset counts were significantly correlated with T-cell functionality in older children, whereas no such correlation was observed in younger ones.

Conclusions: This study demonstrated the potential application of the WB-IGRA approach in evaluating and monitoring T-cell IR in pediatric allo-HSCT recipients. Combining the assessment of T-cell immune functionality with cellular phenotypes could enhance the understanding of T-cell IR in HSCT children of different ages.

Keywords: Pediatric patients; T-cell functionality; allogeneic hematopoietic stem cell transplantation (allo-HSCT); immune reconstitution (IR).

Figure 1

The global T-cell functionality of allo-HSCT children in different post-transplant periods (≤6 months post-trans, >6 and ≤12 months post-trans and >12 months post-trans) (A) and those with different immunosuppressant usage status (in use, decrease in use and out of use) (B). allo-HSCT, allogeneic hematopoietic stem cell transplantation; IFN-γ, interferon-gamma; RFV, relative fluorescent value.

Figure 2

The numbers of T cell subsets, including CD3+ (A), CD4+ (B), CD8+ (C), and the global T cell functionality (D) of pediatric allo-HSCT patients in different post-transplant periods (≤6 months post-trans, >6 and ≤12 months post-trans and >12 months post-trans). The patients were divided into those ≤10 (blank) and >10 (twill) years of age. allo-HSCT, allogeneic hematopoietic stem cell transplantation; IFN-γ, interferon-gamma; RFV, relative fluorescent value.

Figure 3

The correlation between the numbers of T cell subsets, including CD3+ (A,E), CD4+ (B,F), CD8+ (C,G), and global T cell functionality (D,H), along with the post-transplant time in pediatric allo-HSCT patients ≤10 (upper) and >10 (bottom) years of age. allo-HSCT, allogeneic hematopoietic stem cell transplantation; IFN-γ, interferon-gamma; RFV, relative fluorescent value.

Figure 4

The correlation between global T cell functionality and the numbers of T cell subsets, including CD3⁺ (A,D), CD4⁺ (B,E), CD8⁺ (C,D), in pediatric allo-HSCT patients ≤10 (upper) and >10 (bottom) years of age. allo-HSCT, allogeneic hematopoietic stem cell transplantation; IFN-γ, interferon-gamma; RFV, relative fluorescent value.