Cyclosporine A drives a Th17- and Th2-mediated posttransplant obliterative airway disease
| Autor: | Myriam Remmelink, Philippe Lemaitre, Michel Goldman, B. Vokaer, Yoichiro Iwakura, Marc Estenne, Kenneth A. Field, Louis-Marie Charbonnier, A. Le Moine, Oberdan Leo |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Graft Rejection
Transplantation Heterotopic medicine.medical_treatment Lymphocyte Blotting Western Bronchiolitis obliterans Real-Time Polymerase Chain Reaction Immunoenzyme Techniques Interferon-gamma Mice Th2 Cells Immunity In vivo medicine Immunology and Allergy Lung transplantation Animals Transplantation Homologous Pharmacology (medical) RNA Messenger Bronchiolitis Obliterans Mice Knockout Transplantation Mice Inbred BALB C business.industry Reverse Transcriptase Polymerase Chain Reaction Interleukin-17 medicine.disease Flow Cytometry Mice Inbred C57BL Trachea Cytokine medicine.anatomical_structure Immunology Cyclosporine Cytokines Interleukin-4 Lymphocyte Culture Test Mixed business CD8 Immunosuppressive Agents Lung Transplantation |
| Zdroj: | American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 13(3) |
| ISSN: | 1600-6143 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text