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

• DOI: 10.1097/shk.0b013e31811ff60c
• Publication Date: 2009-03-05T06:44:07Z
• Authors: Julia M. Tulley; Jessica L. Palmer; Richard L. Gamelli; Douglas E. Faunce
• Keywords: CD4-Positive T-Lymphocytes; Male; Mice, Inbred BALB C; T-Lymphocytes; Galactosylceramides; Flow Cytometry; 3. Good health; Antigens, CD1; Killer Cells, Natural; Interferon-gamma; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Interleukin-2; Interleukin-4; Antigens, CD1d; CD40 Antigens; Burns; Cell Proliferation

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-gamma. alpha-Galactosylceramide (alpha-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-gamma production. Here, we confirmed the role of Valpha14-Jalpha281 invariant NKT cells in mouse model of burn injury-induced suppression of T-cell immunity and further asked whether alpha-GalCer can improve immunity after injury via similar mechanisms. We observed that systemic treatment with alpha-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-gamma. Moreover, burn injury was associated with diminished expression of major histocompatibility complex II and CD40 on antigen presenting cells that were both restored by alpha-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.