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.

Autor:	Kielsen K; Hematopoietic Stem Cell Transplantation and Primary Immune Deficiency, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; katrinekielsen@dadlnet.dk.; Institute for Inflammation Research, Department of Rheumatology and Spine Disease, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; and., Oostenbrink LVE; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., von Asmuth EGJ; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., Jansen-Hoogendijk AM; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., van Ostaijen-Ten Dam MM; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., Ifversen M; Hematopoietic Stem Cell Transplantation and Primary Immune Deficiency, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Heilmann C; Hematopoietic Stem Cell Transplantation and Primary Immune Deficiency, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark., Schilham MW; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., van Halteren AGS; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., Bredius RGM; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., Lankester AC; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., Jol-van der Zijde CM; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., van Tol MJD; Laboratory of Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands., Müller K; Hematopoietic Stem Cell Transplantation and Primary Immune Deficiency, Department of Pediatrics and Adolescent Medicine, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Institute for Inflammation Research, Department of Rheumatology and Spine Disease, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; and.
Jazyk:	angličtina
Zdroj:	Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2021 Jun 15; Vol. 206 (12), pp. 2828-2838. Date of Electronic Publication: 2021 Jun 09.
DOI:	10.4049/jimmunol.2001077
Abstrakt:	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. (Copyright © 2021 by The American Association of Immunologists, Inc.)
Databáze:	MEDLINE
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