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

Kraetzel, K. and Stoelcker, B. and Eissner, G. and Multhoff, G. and Pfeifer, M. and Holler, E. and Schulz, C. (2008) NKG2D-dependent effector function of bronchial epithelium-activated alloreactive T-cells. EUROPEAN RESPIRATORY JOURNAL, 32 (3). pp. 563-570. ISSN 0903-1936,

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: VERSUS-HOST-DISEASE; ACUTE LUNG INJURY; ALLOGRAFT-REJECTION; NKG2D; TRANSPLANTATION; LYMPHOCYTES; EXPRESSION; PATHWAYS; RECEPTOR; TARGET; alloreaction; CD8 T-cells; lung; major histocompatibility complex I; natural killer group 2 member D
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Medicine > Lehrstuhl für Innere Medizin II
Depositing User: Dr. Gernot Deinzer
Date Deposited: 26 Oct 2020 07:56
Last Modified: 26 Oct 2020 07:56
URI: https://pred.uni-regensburg.de/id/eprint/30348

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