Innate immune activation by the viral PAMP poly I:C potentiates pulmonary graft-versus-host disease after allogeneic hematopoietic cell transplant

Transpl Immunol. 2011 Jan 15;24(2):83-93. doi: 10.1016/j.trim.2010.11.004. Epub 2010 Nov 9.


Respiratory viral infections cause significant morbidity and increase the risk for chronic pulmonary graft-versus-host disease (GVHD) after hematopoietic cell transplantation (HCT). Our overall hypothesis is that local innate immune activation potentiates adaptive alloimmunity. In this study, we hypothesized that a viral pathogen-associated molecular pattern (PAMP) alone can potentiate pulmonary GVHD after allogeneic HCT. We, therefore, examined the effect of pulmonary exposure to polyinosinic:polycytidylic acid (poly I:C), a viral mimetic that activates innate immunity, in an established murine HCT model. Poly I:C-induced a marked pulmonary T cell response in allogeneic HCT mice as compared to syngeneic HCT, with increased CD4+ cells in the lung fluid and tissue. This lymphocytic inflammation persisted at 2 weeks post poly I:C exposure in allogeneic mice and was associated with CD3+ cell infiltration into the bronchiolar epithelium and features of epithelial injury. In vitro, poly I:C enhanced allospecific proliferation in a mixed lymphocyte reaction. In vivo, poly I:C exposure was associated with an early increase in pulmonary monocyte recruitment and activation as well as a decrease in CD4+FOXP3+ regulatory T cells in allogeneic mice as compared to syngeneic. In contrast, intrapulmonary poly I:C did not alter the extent of systemic GVHD in either syngeneic or allogeneic mice. Collectively, our results suggest that local activation of pulmonary innate immunity by a viral molecular pattern represents a novel pathway that contributes to pulmonary GVHD after allogeneic HCT, through a mechanism that includes increased recruitment and maturation of intrapulmonary monocytes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • CD3 Complex
  • CD4-Positive T-Lymphocytes / immunology
  • Flow Cytometry
  • Graft vs Host Disease / immunology*
  • Hematopoietic Stem Cell Transplantation*
  • Immunity, Innate*
  • Lung / immunology*
  • Lung Diseases / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / immunology*
  • Monocytes, Activated Killer / immunology
  • Poly I-C / immunology*
  • Respiratory Mucosa / immunology
  • Respiratory Tract Infections / virology
  • T-Lymphocytes, Regulatory / immunology
  • Transplantation, Homologous


  • CD3 Complex
  • Poly I-C