PREVENTION OF INJURY-INDUCED SUPPRESSION OF T-CELL IMMUNITY BY THE Cd1d/NKT CELL-SPECIFIC LIGAND α-GALACTOSYLCERAMIDE

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Abstract
Infection, sepsis, and multiple organ failure continue to be significant factors leading to morbidity and mortality after severe injury. Studies by our laboratory and others have identified injury-induced defects in both innate and adaptive components of host defense. We previously reported that CD1d-restricted natural killer T (NKT) cells actively suppress effector T-cell immunity after burn injury via production of excess IL-4 and failure to produce IFN-γ. α-Galactosylceramide (α-GalCer) is a synthetic NKT cell-specific ligand presented exclusively to invariant NKT cells and is known to improve immunity against tumors and infection by promoting IFN-γ production. Here, we confirmed the role of Vα14-Jα281 invariant NKT cells in mouse model of burn injury-induced suppression of T-cell immunity and further asked whether α-GalCer can improve immunity after injury via similar mechanisms. We observed that systemic treatment with α-GalCer prevented the injury-induced suppression of Ag-specific T-cell responsiveness both in vitro and in vivo and restored the ability of splenic lymphocytes to produce both IL-2 and IFN-γ. Moreover, burn injury was associated with diminished expression of major histocompatibility complex II and CD40 on antigen presenting cells that were both restored by α-GalCer treatment to levels seen in sham-treated mice. Collectively, these data suggest that, via manipulation of the NKT cell population, we may be able to maintain T-cell function and improve host defense after burn injury.