PT - JOURNAL ARTICLE AU - K. Kraetzel AU - B. Stoelcker AU - G. Eissner AU - G. Multhoff AU - M. Pfeifer AU - E. Holler AU - C. Schulz TI - NKG2D-dependent effector function of bronchial epithelium-activated alloreactive T-cells AID - 10.1183/09031936.00096407 DP - 2008 Sep 01 TA - European Respiratory Journal PG - 563--570 VI - 32 IP - 3 4099 - http://erj.ersjournals.com/content/32/3/563.short 4100 - http://erj.ersjournals.com/content/32/3/563.full SO - Eur Respir J2008 Sep 01; 32 AB - 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-γ, 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.