DX5+ NKT cells induce the death of colitis-associated cells: involvement of programmed death ligand-1.
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.
Hornung
Matthias
M
Department of Surgery, University of Regensburg, Regensburg, Germany. matthias.hornung@klinik.uni-regensburg.de
Farkas
Stefan A
SA
Sattler
Christine
C
Schlitt
Hans J
HJ
Geissler
Edward K
EK
D019264:Adoptive Transfer; D000818:Animals; D018949:Antigens, CD1 / Q000096:biosynthesis; D055610:Antigens, CD1d; D018122:B7-1 Antigen / Q000502:physiology*; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016923:Cell Death; D003092:Colitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007694:Killer Cells, Natural / Q000502:physiology*; D019041:L-Selectin / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010455:Peptides / Q000502:physiology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D019041:L-Selectin