NKG2D-dependent effector function of bronchial epithelium-activated alloreactive T-cells.
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.
Kraetzel
K
K
Dept of Internal Medicine II, University of Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93053 Germany.
Stoelcker
B
B
Eissner
G
G
Multhoff
G
G
Pfeifer
M
M
Holler
E
E
Schulz
C
C
D055371:Acute Lung Injury / Q000209:etiology / Q000503:physiopathology*; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*
C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K