| Title: |
Bone Marrow-Suppressive Treatment in Children Is Associated with Diminished IFN-γ Response from T Cells upon Polyclonal and Varicella Zoster Virus Peptide Stimulation |
| Authors: |
Tiselius, Eva; Sundberg, Emil; Andersson, Hanna; Höbinger, Anna; Jahnmatz, Peter; Harila, Arja; Palle, Josefine; Nilsson, Anna; Saghafian-Hedengren, Shanie |
| Publisher Information: |
Uppsala universitet, Barnonkologisk och neurologisk forskning; Karolinska Inst, Dept Womens & Childrens Hlth, Div Pediat Oncol & Pediat Surg, S-17177 Stockholm, Sweden.; Mabtech AB, S-13152 Nacka Strand, Sweden.; Uppsala Univ Hosp, Dept Childrens Oncol & Hematol, S-751 85 Uppsala, Sweden. |
| Publication Year: |
2024 |
| Collection: |
Uppsala University: Publications (DiVA) |
| Subject Terms: |
memory T cell; varicella; IFN-gamma; children; lymphoid malignancy; Immunology in the medical area; Immunologi inom det medicinska området; Pediatrics; Pediatrik |
| Description: |
Severe haematological diseases and lymphoid malignancies require bone marrow (BM)-suppressive treatments. Knowledge regarding the impact of BM-suppressive treatments on children's memory T cells is very limited. Memory T cells play a crucial role in defending against herpesviruses, which is particularly relevant in paediatric cancer care. We studied 53 children in total; 34 with cancer and 2 with severe haematological disorders, with some receiving BM-suppressive treatment with or without allogeneic-haematopoietic stem cell transplantation (allo-HSCT), alongside 17 healthy controls. We focused on peripheral blood proportions of memory T-cell subsets using flow cytometry and analysed cytokine-secreting T cells with a four-parameter FluoroSpot assay in response to T-cell mitogen and varicella zoster virus (VZV) peptides. Patients on BM-suppressive treatment showed increased clusters of differentiation (CD)4+ and CD8+ effector memory (TEM)/terminally differentiated effector (TEFF) T cells compared to the healthy controls. They also exhibited, amongst other things, when compared to the healthy controls, a reduced total number of cytokine-secreting cells, by means of interferon (IFN)-γ, interleukin (IL)-17A, IL-10, and IL-22, following mitogen activation. A diminished IFN-γ response among the children with BM-suppressive treatment was observed upon VZV-peptide stimulation, compared to the healthy children. Collectively, the findings herein indicate that the children who are undergoing or have finished BM-suppressive treatment display qualitative differences in their T-cell memory compartment, potentially increasing their susceptibility to severe viral infections and impacting their immunotherapy, which relies on the functional ability of autologous T cells. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
International Journal of Molecular Sciences, 1661-6596, 2024, 25:13; PMID 39000070; ISI:001269683900001 |
| DOI: |
10.3390/ijms25136960 |
| Availability: |
http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-535972; https://doi.org/10.3390/ijms25136960 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.CED3BCB6 |
| Database: |
BASE |