title: CD4+ T cell counts reflect the immunosuppressive state of CD4 helper cells in patients after allogeneic stem cell transplantation.
abstract: The recovery of the host immune system after allogeneic hematopoietic stem cell transplantation is pivotal to prevent infections, relapse, and secondary malignancies. In particular, numerical CD4+ T cells reconstitution is delayed and CD4 helper cell function is considered impaired as a consequence of the transplant procedure and concomitant immunosuppressive medication. From HIV/AIDS patients, it is known that numerical and functional CD4 defects increase the risk of opportunistic infections. However, and in contrast to patients with HIV, anti-infective prophylaxis after allogeneic transplantation is usually given for 6 months depending on immunosuppressive medication and existing graft-versus-host disease but independently of absolute CD4+ T cells counts. We hypothesized that a qualitative T cell defect is existing after allogeneic transplantation, especially in patients with delayed immune-reconstitution. Applying transcriptional as well as functional approaches, we show that CD4+ T cells with delayed recovery have a distinct transcriptional profile and cluster differently from T cells originated from patients with completed immune recovery. Moreover, inhibitory signatures are substantially enriched within the transcriptional profile of these T cells translating to functional defects and impaired interleukin 2 production. In addition to time after transplant, CD4+ T cells numbers should be considered for the decision to stop or maintain antimicrobial prophylaxis in patients after allogeneic stem cell transplantation.
authors.affiliation: Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany, udo.holtick@uk-koeln.de.
authors.forename: Udo
authors.initials: U
authors.lastname: Holtick
authors.forename: Lukas P
authors.initials: LP
authors.lastname: Frenzel
authors.forename: Alexander
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Theurich
authors.forename: Julia
authors.initials: J
authors.lastname: Claasen
authors.forename: Christof
authors.initials: C
authors.lastname: Scheid
authors.forename: Michael
authors.initials: M
authors.lastname: von Bergwelt-Baildon
authors.forename: Holger
authors.initials: H
authors.lastname: Fröhlich
authors.forename: Clemens M
authors.initials: CM
authors.lastname: Wendtner
authors.forename: Jens M
authors.initials: JM
authors.lastname: Chemnitz
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000639:trends*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000639:trends; D055815:Young Adult