title: Impact of systemic immuno-suppression after solid organ transplantation on allergen-specific responses.
abstract: BACKGROUND
  The immunosuppressive therapy in solid organ transplantation targets mainly the T- and B-cell-mediated immune response. However, there is evidence that it neither suppresses sensitization nor clinical manifestation of allergic diseases in organ-transplanted patients.
  
  
  OBJECTIVE
  This study addresses the question whether allergen-specific responses are altered by systemic immunosuppression via negative effects on the T-regulatory cell compartment and a more pronounced suppression on Th1-type T-cell responses.
  
  
  METHODS
  Peripheral blood mononuclear cells from 65 solid organ-transplanted (kidney, liver, lung) children, adolescents, and young adults and 18 healthy, matched controls were included, and their clinical and sensitization status assessed. Allergen-specific proliferation, intracellular cytokine production, frequency of forkhead box P3 (FOXP3)+ CD3+ CD4+ CD25(high) cells, mRNA expression of IL-10, transforming growth factor (TGF)-β and FOXP3 (real-time RT-PCR) of peripheral blood mononuclear cells or bronchoalveolar lavage fluid (BAL)-derived cells, and the inhibitory capacity of T-reg cells were investigated.
  
  
  RESULTS
  Immunosuppression led to a significantly altered regulatory marker profile expressed by enhanced TGF-β mRNA production and a reduced frequency of FOXP3+ CD4+ CD3+ cells in solid organ transplanted individuals. FOXP3 expression in BAL cells of lung-transplanted patients was significantly decreased. Allergen-specific proliferation was not significantly altered despite long-term immunosuppression. However, suppression of allergen-specific responses via the T-regulatory cell fraction was deficient in immunosuppressed individuals.
  
  
  CONCLUSIONS
  The results suggest an insufficient control of allergen-specific responses via the Treg-cell compartment under systemic immunosuppression.
authors.affiliation: Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Eiwegger
authors.forename: S
authors.initials: S
authors.lastname: Gruber
authors.forename: C
authors.initials: C
authors.lastname: Geiger
authors.forename: E
authors.initials: E
authors.lastname: Mayer
authors.forename: E
authors.initials: E
authors.lastname: Dehlink
authors.forename: C
authors.initials: C
authors.lastname: Bannert
authors.forename: T
authors.initials: T
authors.lastname: Frischer
authors.forename: D
authors.initials: D
authors.lastname: Kasper
authors.forename: P
authors.initials: P
authors.lastname: Jaksch
authors.forename: W
authors.initials: W
authors.lastname: Klepetko
authors.forename: C
authors.initials: C
authors.lastname: Akdis
authors.forename: Z
authors.initials: Z
authors.lastname: Szépfalusi
mesh_terms: D000293:Adolescent; D000485:Allergens / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D016207:Cytokines / Q000235:genetics; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology*; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D016377:Organ Transplantation / Q000009:adverse effects*; D012333:RNA, Messenger / Q000032:analysis; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D000485:Allergens; D016207:Cytokines; D012333:RNA, Messenger