title: Regulatory T Cells in Chronic Graft-Versus-Host Disease After Extracorporeal Photopheresis: Correlation With Skin and Global Organ Responses, and Ability to Taper Steroids.
abstract: BACKGROUND
  Induction of immune tolerance by an increase in regulatory T (Treg) cells after extracorporeal photopheresis (ECP) is thought to contribute to how ECP exerts its therapeutic effect in patients with chronic graft-versus-host disease (cGvHD). We investigated whether percentages and absolute counts of Treg cells changed post-ECP, and examined correlation with response.
  
  
  METHODS
  Absolute counts and % of CD4+ T cells and Treg cells (CD4 + CD25 + FOXP3 + CD127dim/-) were evaluated using flow cytometry in 32 patients with cGvHD treated by ECP for a minimum of 3 months, and up to 12 months. CD4+ or Treg cells at baseline to 12 months post-ECP were compared with changes in skin disease scores or global organ involvement, or the ability to taper steroids, at 14, 28, and 56 weeks.
  
  
  RESULTS
  Regulatory T cells % increased significantly above any overall changes in CD4+ % at 6, 9, and 12 months post-ECP. There was no statistically significant association between Treg cells and skin or steroid response, whereas a larger increase in CD4+ count from baseline to 1 to 3 months corresponded to increased odds of being able to reduce steroid dose by 50% or greater at 14 weeks. Skin and global organ responders at 28 weeks had higher median Treg cell counts 3 months post-ECP than nonresponders, as did steroid responders at 56 weeks who were 12 months post-ECP.
  
  
  CONCLUSIONS
  Regulatory T cell counts and % varied greatly among cGvHD patients, and the increase post-ECP was not significant until 6 months. No clear correlation was found between Treg cells and clinical improvement, suggesting that increases in Treg cell numbers and/or proportions are not driving the mechanism leading to a response after ECP.
authors.affiliation: 1 Haematology Department and Photopheresis Unit, Rotherham NHS Foundation Trust, Rotherham, South Yorkshire, United Kingdom. 2 Medical Statistics Group, School of Health and Related Research (ScHARR), The University of Sheffield Sheffield, South Yorkshire, United Kingdom. 3 Knowledge and Intelligence Team (East Midlands), Public Health England, Sheffield, United Kingdom.
authors.forename: Helen A
authors.initials: HA
authors.lastname: Denney
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Whittle
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lai
authors.forename: Richard M
authors.initials: RM
authors.lastname: Jacques
authors.forename: Peter C
authors.initials: PC
authors.lastname: Taylor
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D002908:Chronic Disease; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017893:Photopheresis / Q000009:adverse effects; D012867:Skin / Q000187:drug effects* / Q000276:immunology; D013256:Steroids / Q000008:administration & dosage* / Q000009:adverse effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids