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Open Access Research

Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production

Heather L Benson12, Hidemi Suzuki123, Jeremy Lott12, Amanda Jo Fisher124, Crystal Walline12, Kathleen M Heidler12, Randy Brutkiewicz12, Janice S Blum12 and David S Wilkes12*

Author Affiliations

1 Department of Medicine, Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

2 Center for Immunobiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

3 Department of Thoracic Surgery, Chiba University, Chiba, Japan

4 Department of Anesthesia, Indiana University School of Medicine, Indianapolis, IN 46202, USA

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Respiratory Research 2012, 13:25  doi:10.1186/1465-9921-13-25

Published: 20 March 2012

Abstract

Background

Direct allorecognition, i.e., donor lung-derived dendritic cells (DCs) stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs) and plasmacytoid (pDCs) are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown.

Methods

Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2d) prior to transplanting into C57BL/6 mice (H-2b), followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+).

Results

Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFN╬│, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production.

Conclusion

Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.

Keywords:
Lung transplantation; dendritic cells; mouse; T cell activation