IL-7 and IL-15 levels reflect the degree of T cell depletion during lymphopenia and are associated with an expansion of effector memory T cells after pediatric hematopoietic stem cell transplantation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Katrine Kielsen
  • Lisa V.E. Oostenbrink
  • Erik G.J. Von Asmuth
  • Anja M. Jansen-Hoogendijk
  • Monique M. Van Ostaijen-Ten Dam
  • Marianne Ifversen
  • Carsten Heilmann
  • Marco W. Schilham
  • Astrid G.S. Van Halteren
  • Robbert G.M. Bredius
  • Arjan C. Lankester
  • Cornelia M. Jol-Van Der Zijde
  • Maarten J.D. Van Tol
  • Muller, Klaus

Differentially and functionally distinct T cell subsets are involved in the development of complications after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about factors regulating their recovery after HSCT. In this study, we investigated associations between immune-regulating cytokines, T cell differentiation, and clinical outcomes. We included 80 children undergoing allogeneic HSCT for acute leukemia using bone marrow or peripheral blood stem cells grafted from a matched sibling or unrelated donor. Cytokines (IL-7, IL-15, IL-18, SCF, IL-6, IL-2, and TNF-α) and active anti-thymocyte globulin (ATG) levels were longitudinally measured along with extended T cell phenotyping. The cytokine profiles showed a temporary rise in IL-7 and IL-15 during lymphopenia, which was strongly dependent on exposure to active ATG. High levels of IL-7 and IL-15 from graft infusion to day +30 were predictive of slower T cell recovery during the first 2 mo post-HSCT; however, because of a major expansion of memory T cell stages, only naive T cells remained decreased after 3 mo (p < 0.05). No differential effect was seen on polarization of CD4+ T cells into Th1, Th2, or Th17 cells or regulatory T cells. Low levels of IL-7 and IL-15 at day +14 were associated with acute graft-versus-host disease grades II-IV in ATG-treated patients (p = 0.0004 and p = 0.0002, respectively). Children with IL-7 levels comparable to healthy controls at day +14 post-HSCT were less likely to develop EBV reactivation posttransplant. These findings suggest that quantification of IL-7 and IL-15 may be useful as biomarkers in assessing the overall T cell depletion and suggest a potential for predicting complications after HSCT.

OriginalsprogEngelsk
TidsskriftJournal of Immunology
Vol/bind206
Udgave nummer12
Sider (fra-til)2828-2838
Antal sider11
ISSN0022-1767
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
This work was supported by the Research Council at Copenhagen University Hospital Rigshospitalet (Grant R85-A3157), The Danish Childhood Cancer Association (Grant 2015-30), the Dagmar Marshalls Fond, and The Netherlands Organization for Health Research and Development (Grant 40-41500-98-11044). The authors alone are responsible for the content and writing of the paper.

Publisher Copyright:
Copyright ©2021 by TheAmericanAssociation of Immunologists, Inc.

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