NKG2D-dependent effector function of bronchial epithelium-activated alloreactive T-cells

Eur Respir J. 2008 Sep;32(3):563-70. doi: 10.1183/09031936.00096407. Epub 2008 Apr 16.


Allogeneic haematopoietic stem cell transplantation (SCT) has emerged as a curative therapeutic option. However, the role of graft-versus-host disease in lung injury after SCT has yet to be determined. In the present study, primary bronchial epithelial cells and the bronchial epithelial cell line BEAS-2B were used to investigate immune responses of allogeneic CD8+ T-cells directed against respiratory epithelial cells. Following stimulation with irradiated bronchial epithelial cells, CD8+ T-cells produced significant amounts of interferon-gamma, upregulated alloantigen activation markers and proliferated highly compared with T-cells stimulated with interleukin-2 alone. Furthermore, cytotoxicity assays demonstrated that bronchial epithelial cell-specific and granzyme B-mediated cytolytic activity was induced in CD8+ T-cells. Generation of natural killer (NK) T-cells, NK-like T-cells, cytokine-induced killer cells or lymphokine-activated killer cells could be excluded by phenotyping, culture conditions and neglectable lytic activity following stimulation with interleukin-2 alone. Inhibition experiments showed that lysis of bronchial epithelial cells was not major histocompatibility complex-I restricted, but depended on NK group 2 member D signalling; a stimulatory receptor initially shown to be expressed on NK cells. The present data imply that the respiratory epithelium has an antigen presenting function and directly alloactivates cytotoxic CD8+ T-cells that show nonclassical effector function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / etiology
  • Acute Lung Injury / physiopathology*
  • Antigen-Presenting Cells / cytology*
  • Antigen-Presenting Cells / physiology
  • Cell Line
  • Cells, Cultured
  • Coculture Techniques
  • Epithelial Cells / physiology*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • NK Cell Lectin-Like Receptor Subfamily K / physiology*
  • T-Lymphocytes, Cytotoxic / physiology*


  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K