title: Reconstitution of interleukin-17-producing T helper cells after allogeneic hematopoietic cell transplantation.
abstract: Interleukin 17A (IL-17)-producing CD4(+) T helper type 17 (Th17) cells have recently drawn attention as possible effector cells of acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) in murine models. Their role after allogeneic HCT in humans is unknown. In this prospective study, Th17, Th1/17, and Th1 cells were quantified in the peripheral blood of 80 patients within the first 3 months after allogeneic HCT using intracellular cytokine staining and flow cytometry. Within the observation period, Th1, Th1/17, and Th17 cells did not reconstitute to levels of healthy control subjects. In contrast to Th1 cells, no further expansion of Th1/17 and Th17 cells was observed during the first month after HCT. Antithymocyte globulin during conditioning significantly reduced the frequency of Th1/17 and Th17 cells but not of Th1 cells. Acute GVHD was not associated with significant changes in the size of the Th1, Th1/17, or Th17 cell subsets. Cytomegalovirus reactivation triggered the expansion of all T helper subsets, and Th1 cells showed the strongest increase. In contrast, no significant changes were found in the T helper cell compartment of patients with bacterial infections compared with time-matched control subjects. In conclusion, quantitative reconstitution of Th1, Th1/17, and Th17 cells is impaired within the first 3 months after HCT, especially when antithymocyte globulin is administered during conditioning. Cytomegalovirus reactivation, but not acute GVHD or bacterial infection, triggered the absolute expansion of these T cell subsets.
authors.affiliation: Department of Medicine I, University Hospital Carl Gustav Carus, Fetscherstrasse 74, Dresden, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Bahr
authors.forename: Rebekka
authors.initials: R
authors.lastname: Wehner
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.forename: Martin
authors.initials: M
authors.lastname: Wermke
authors.forename: Nona
authors.initials: N
authors.lastname: Shayegi
authors.forename: Jan Moritz
authors.initials: JM
authors.lastname: Middeke
authors.forename: Christoph
authors.initials: C
authors.lastname: Röllig
authors.forename: Johannes
authors.initials: J
authors.lastname: Schetelig
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Marc
authors.initials: M
authors.lastname: Schmitz
authors.forename: Martin
authors.initials: M
authors.lastname: Bornhäuser
authors.forename: Sebastian
authors.initials: S
authors.lastname: Tuve
mesh_terms: D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000494:pharmacology / Q000627:therapeutic use; D001424:Bacterial Infections / Q000276:immunology / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003586:Cytomegalovirus Infections / Q000276:immunology / Q000473:pathology*; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control; D006402:Hematologic Diseases / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D000961:Antilymphocyte Serum; C508717:IL17A protein, human; D020381:Interleukin-17; D019653:Myeloablative Agonists