CD4 T cells but not Th17 cells are required for mouse lung transplant obliterative bronchiolitis

Q. Wu, P. K. Gupta, H. Suzuki, S. R. Wagner, C. Zhang, Oscar Cummings, L. Fan, Mark Kaplan, D. S. Wilkes, R. A. Shilling

Research output: Contribution to journalArticle

22 Citations (Scopus)

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<sup>+</sup> T cells and γδ T cells. Depletion of CD4<sup>+</sup> T cells led to a significantly decreased frequency and number of IL-17A<sup>+</sup> 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<sup>+</sup> cells was not decreased in mice with STAT3-deficient T cells due mainly to the presence of IL-17A<sup>+</sup> γδ T cells. Deficiency of γδ T cells also did not affect the development of airway fibrosis. Our data suggest that CD4<sup>+</sup> 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. This study finds that CD4+ T cell deficiency attenuates the IL-17 immune response and prevents lung transplant obliterative bronchiolitis in a mouse model, but the absence of either major source of IL-17, Th17 cells or yδ T cells, is not sufficient to prevent allograft rejection and airway fibrosis.

Original languageEnglish
Pages (from-to)1793-1804
Number of pages12
JournalAmerican Journal of Transplantation
Volume15
Issue number7
DOIs
StatePublished - Jul 1 2015

Fingerprint

Th17 Cells
Bronchiolitis
Interleukin-17
T-Lymphocytes
Transplants
Lung
Allografts
Fibrosis
Lung Transplantation

Keywords

  • animal models: murine
  • basic (laboratory) research/science
  • biology
  • bronchiolitis obliterans (BOS)
  • immunobiology
  • lung (allograft) function/dysfunction
  • lung transplantation/pulmonology
  • T cell

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

CD4 T cells but not Th17 cells are required for mouse lung transplant obliterative bronchiolitis. / Wu, Q.; Gupta, P. K.; Suzuki, H.; Wagner, S. R.; Zhang, C.; Cummings, Oscar; Fan, L.; Kaplan, Mark; Wilkes, D. S.; Shilling, R. A.

In: American Journal of Transplantation, Vol. 15, No. 7, 01.07.2015, p. 1793-1804.

Research output: Contribution to journalArticle

Wu, Q, Gupta, PK, Suzuki, H, Wagner, SR, Zhang, C, Cummings, O, Fan, L, Kaplan, M, Wilkes, DS & Shilling, RA 2015, 'CD4 T cells but not Th17 cells are required for mouse lung transplant obliterative bronchiolitis', American Journal of Transplantation, vol. 15, no. 7, pp. 1793-1804. https://doi.org/10.1111/ajt.13215
Wu, Q. ; Gupta, P. K. ; Suzuki, H. ; Wagner, S. R. ; Zhang, C. ; Cummings, Oscar ; Fan, L. ; Kaplan, Mark ; Wilkes, D. S. ; Shilling, R. A. / CD4 T cells but not Th17 cells are required for mouse lung transplant obliterative bronchiolitis. In: American Journal of Transplantation. 2015 ; Vol. 15, No. 7. pp. 1793-1804.
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