Open Access Green as soon as Postprint is submitted to ZB.
NKG2D-dependent effector function of bronchial epithelium activated alloreactive T cells.
Eur. Respir. J. 32, 1-8 (2008)
Allogeneic hematopoietic 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 still 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 IFN-gamma, upregulated alloantigen activation markers and proliferated highly compared to T-cells stimulated with IL-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 NK-, NK-like T cells (NKT cells), cytokine-induced killer (CIK) or lymphokine activated killer (LAK) cells could be excluded by phenotyping, culture conditions and neglectable lytic activity following stimulation with IL-2 alone. Inhibition experiments showed that lysis of bronchial epithelial cells was not MHC I restricted but depended on natural killer group 2, member D (NKG2D) signaling, a stimulatory receptor initially shown to be expressed on NK cells.Our data imply that respiratory epithelium has antigen presenting function and directly alloactivates cytotoxic CD8(+) T cells which show nonclassical effector function.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Alloreaction; CD8 T cells; lung; MHC I; NKG2D
ISSN (print) / ISBN
0903-1936
e-ISSN
1399-3003
Journal
European Respiratory Journal
Quellenangaben
Volume: 32,
Issue: 3,
Pages: 1-8
Publisher
European Respiratory Society
Publishing Place
Sheffield
Reviewing status
Peer reviewed
Institute(s)
CCG Innate Immunity in Tumor Biology (PATH-KTB)