RT Journal Article
SR Electronic
T1 NKG2D-dependent effector function of bronchial epithelium-activated alloreactive T-cells
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 563
OP 570
DO 10.1183/09031936.00096407
VO 32
IS 3
A1 K. Kraetzel
A1 B. Stoelcker
A1 G. Eissner
A1 G. Multhoff
A1 M. Pfeifer
A1 E. Holler
A1 C. Schulz
YR 2008
UL http://erj.ersjournals.com/content/32/3/563.abstract
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.