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Keywords:

  • allergy;
  • children;
  • cyclosporin A;
  • IgE;
  • immunosuppression;
  • rapamycin;
  • regulatory T-cells;
  • tacrolimus;
  • transplantation

To cite this article: Eiwegger T, Gruber S, Geiger C, Mayer E, Dehlink E, Bannert C, Frischer T, Kasper D, Jaksch P, Klepetko W, Akdis C, Szépfalusi Z. Impact of systemic immuno-suppression after solid organ transplantation on allergen-specific responses. Allergy 2011; 66: 271–278.

Abstract

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+CD25high 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.