INTRODUCTION: 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. MATERIAL AND 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. CONCLUSION: The results suggest an insufficient control of allergen-specific responses via the Treg-cell compartment under systemic immunosuppression.
INTRODUCTION: 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. MATERIAL AND 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. CONCLUSION: The results suggest an insufficient control of allergen-specific responses via the Treg-cell compartment under systemic immunosuppression.
Authors: Michael B Soyka; David Holzmann; Tomasz M Basinski; Marcin Wawrzyniak; Christina Bannert; Simone Bürgler; Tunc Akkoc; Angela Treis; Beate Rückert; Mübeccel Akdis; Cezmi A Akdis; Thomas Eiwegger Journal: PLoS One Date: 2015-05-01 Impact factor: 3.240