Hornung, Matthias and Farkas, Stefan A. and Sattler, Christine and Schlitt, Hans J. and Geissler, Edward K. (2006) DX5+ NKT cells induce the death of colitis-associated cells: involvement of programmed death ligand-1. European journal of immunology 36 (5), pp. 1210-1221.
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Other URL: http://dx.doi.org/10.1002/eji.200535332
NKT cells are activated by CD1d and show an immune regulating function. Here, we investigated whether DX5+ NKT cells could be used to reduce colitis in a chronic colitis mouse model and studied the potential immunological mechanisms involved. Chronic colitis was induced either by transfer of enriched CD62L+ CD4+ T cells to severe-combined-immunodeficient mice or by feeding dextran sodium sulfate to immune competent mice. DX5+ NKT cells were transferred to mice with chronic colitis. Co-transfer of DX5+ NKT cells, but not CD8+ control cells, prevented the onset of colitis, and the immune regulatory effect of DX5+ NKT cells was completely abrogated by injecting CD1d blocking antibody. Moreover, DX5+ NKT cells reduced established colitis in both chronic colitis models. In vitro, DX5+ NKT cells induced cell death of colon-infiltrating lymphocytes isolated from diseased mice. This effect was inhibited in the presence of either anti-CD1d or anti-programmed death ligand-1 (PD-L1) blocking antibodies. The specific potency of DX5+ NKT cells in regulating chronic colitis in two mouse models is demonstrated. In vitro testing suggests that DX5+ NKT cells activated by CD1d induce cell death of colitis-inducing lymphocytes, which is mediated through PD-L1. Therefore, DX5+ NKT cells could be important in the regulation of immune responses associated with chronic colitis.
|Institutions:||Medicine > Lehrstuhl für Chirurgie|
|Keywords:||CD1d; Cell transfer; Colitis; DX5⁺NKT cells; Programmed death ligand-1|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||02 Mar 2007|
|Last Modified:||20 Jul 2011 20:52|