CD4 T Cells but Not Th17 Cells Are Required for Mouse Lung Transplant Obliterative Bronchiolitis.
Am J Transplant
; 15(7): 1793-1804, 2015 Jul.
Article
en En
| MEDLINE
| ID: mdl-25773063
ABSTRACT
Lung transplant survival is limited by obliterative bronchiolitis (OB), but the mechanisms of OB development are unknown. Previous studies in a mouse model of orthotopic lung transplantation suggested a requirement for IL-17. We have used this orthotopic mouse model to investigate the source of IL-17A and the requirement for T cells producing IL-17A. The major sources of IL-17A were CD4(+) T cells and γδ T cells. Depletion of CD4(+) T cells led to a significantly decreased frequency and number of IL-17A(+) lymphocytes and was sufficient to prevent acute rejection and OB. However, mice with STAT3-deficient T cells, which are unable to differentiate into Th17 cells, rejected lung allografts and developed OB similar to control mice. The frequency of IL-17A(+) cells was not decreased in mice with STAT3-deficient T cells due mainly to the presence of IL-17A(+) γδ T cells. Deficiency of γδ T cells also did not affect the development of airway fibrosis. Our data suggest that CD4(+) T cells are required for OB development and expansion of IL-17A responses in the lung, while Th17 and γδ T cells are not absolutely required and may compensate for each other.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Bronquiolitis Obliterante
/
Linfocitos T CD4-Positivos
/
Trasplante de Pulmón
/
Interleucina-17
/
Células Th17
/
Supervivencia de Injerto
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos