title: The number of T cell allo-epitopes associates with CD4+ and CD8+ T-cell infiltration in pediatric cutaneous GVHD.
abstract: Risk factors for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem-cell transplantation (HCST) include: HLA mismatches, sex-mismatch, and stem-cell source. We retrospectively analyzed if HLA- and sex-mismatching quantitatively affects the composition of GVHD-induced T-cell infiltrates. We quantified absolute numbers of CD4+ and CD8+ T cells present in tissue sections from skin biopsies of 23 pediatric HSCT-recipients with GVHD. HSCT with a sex-mismatched unrelated donor was associated with an increased number of CD4+ T cells when compared to a sex-matched unrelated donor (p=0.01). The absolute numbers of skin-infiltrating T cells were increased in patients expressing T-cell epitopes derived from the recipient's mismatched HLA, so called predicted indirectly recognizable HLA epitopes (PIRCHE). The combined expression of PIRCHE with a sex-mismatch resulted in the highest number of skin-infiltrating T cells. Our results indicate that an increased number of recipient-specific T-cell epitopes is associated with accumulation of CD4+ and CD8+ T cells in the skin.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: k.a.thus@umcutrecht.nl.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Thus
authors.affiliation: Immunology Laboratory/Pediatric Stem Cell Transplantation Unit, Willem Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Astrid G S
authors.initials: AG
authors.lastname: van Halteren
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Titus A P
authors.initials: TA
authors.lastname: de Hond
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Marijke R
authors.initials: MR
authors.lastname: van Dijk
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Robin Q H
authors.initials: RQ
authors.lastname: Kloos
authors.affiliation: Immunology Laboratory/Pediatric Stem Cell Transplantation Unit, Willem Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.affiliation: Department of Hematology and Stem Cell Transplantation, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
authors.forename: Marc B
authors.initials: MB
authors.lastname: Bierings
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Spierings
mesh_terms: D001706:Biopsy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D018709:Statistics, Nonparametric
chemical_list: D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens
keywords: Allogeneic hematopoietic stem-cell transplantation; Cutaneous graft-versus-host disease; HY; PIRCHE; Pediatric; T cells