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

¹ Dept of Internal Medicine II, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
² Dept of Hematology and Oncology, University of Regensburg, Germany. Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany
³ Dept of Radiotherapy and Radiooncology, Klinkum rechts der Isar, Technische Universität München, Germany. Ismaningerstr. 22, 81675 Munich, Germany

^* To whom correspondence should be addressed. E-mail: christian.schulz{at}klinik.uni-regensburg.de.

	Abstract

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-, 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.