A role for CD1d-restricted NKT cells in injury-associated T cell suppression

Journal of Leukocyte Biology

Mashkoor A. Choudhry¹  Elizabeth J. Kovacs²  Richard L. Gamelli¹  Douglas E. Faunce¹ 

[1] The Burn and Shock Trauma Institute, Department of Surgery, and The Burn and Shock Trauma Institute, Department of Surgery, and The Burn and Shock Trauma Institute, Department of Surgery, and;The Burn and Shock Trauma Institute, Department of Surgery, and Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, Illinois The Burn and Shock Trauma Institute, Department of Surgery, and The Burn and Shock Trauma Institute, Department of Surgery, and Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, Illinois Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, Illinois The Burn and Shock Trauma Institute, Department of Surgery, and Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, Illinois

关键词: natural killer T cells;    burns;    immune suppression;   

DOI  :  10.1189/jlb.1102540

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Natural killer T (NKT) cells are known to modulate T cell responses during autoimmunity, tolerance, and antitumor immunity; however, their potential role in regulating the immune response to injury has not been reported. Using a murine model of burn injury, we investigated whether CD1d-restricted NKT cells played a role in the T cell suppression that occurs early after injury. A functional role for CD1d stimulation of NKT cells in the injury-related immune suppression was demonstrated by experiments in which the suppression of antigen (Ag)-specific delayed-type hypersensitivity and in vitro T cell-proliferative responses were prevented if mice were given anti-CD1d monoclonal antibody (mAb) systemically just before injury. The CD1d-NKT cell-dependent suppression of the T cell response after injury occurred in the absence of quantitative changes in NKT cells themselves or CD1d+ Ag-presenting cells. We observed that elevated production of the immunosuppressive cytokine interleukin (IL)-4 correlated with burn-induced immune dysfunction, and we found that NKT cells but not conventional T cells were the source of IL-4 early after injury. Lastly, we observed that the injury-induced production of NKT cell-derived IL-4 could be blocked by systemic treatment of burn-injured mice with anti-CD1d mAb. Together, our results reveal a novel mechanism involving CD1d stimulation of NKT cells in the onset of T cell suppression that occurs subsequent to injury.

【 授权许可】

Unknown