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Kraetzel, K.* ; Stoelcker, B.* ; Eissner, G.* ; Multhoff, G. ; Pfeifer, M.* ; Holler, E.* ; Schulz, C.*

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

Eur. Respir. J. 32, 1-8 (2008)

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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.

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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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