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Cyclosporine A Drives a Th17‐ and Th2‐Mediated Posttransplant Obliterative Airway Disease
Author(s) -
Lemaître P. H.,
Vokaer B.,
Charbonnier L.M.,
Iwakura Y.,
Field K. A.,
Estenne M.,
Goldman M.,
Leo O.,
Remmelink M.,
Moine A. Le
Publication year - 2013
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.12067
Subject(s) - bronchiolitis obliterans , medicine , immunology , cd8 , calcineurin , tacrolimus , lung transplantation , transplantation , cytokine , in vivo , airway , interleukin 17 , graft versus host disease , immune system , biology , microbiology and biotechnology , surgery
Calcineurin‐inhibitor refractory bronchiolitis obliterans (BO) represents the leading cause of late graft failure after lung transplantation. T helper (Th)2 and Th17 lymphocytes have been associated with BO development. Taking advantage of a fully allogeneic trachea transplantation model in mice, we addressed the pathogenicity of Th cells in obliterative airway disease (OAD) occurring in cyclosporine A (CsA)‐treated recipients. We found that CsA prevented CD8 + T cell infiltration into the graft and downregulated the Th1 response but affected neither Th2 nor Th17 responses in vivo . In secondary mixed lymphocyte cultures, CsA dramatically decreased donor‐specific IFN‐γ production, enhanced IL‐17 production and did not affect IL‐13. As CD4 + depletion efficiently prevented OAD in CsA‐treated recipients, we further explored the role of Th2 and Th17 immunity in vivo . Although IL‐4 and IL‐17 deficient untreated mice developed an OAD comparable to wild‐type recipients, a single cytokine deficiency afforded significant protection in CsA‐treated recipients. In conclusion, CsA treatment unbalances T helper alloreactivity and favors Th2 and Th17 as coexisting pathways mediating chronic rejection of heterotopic tracheal allografts.