DENDRITIC CELL-NKT CELL INTERACTIONS ARE REQUIRED FOR IMMUNE SUPPRESSION AFTER INJURY

Abstract

Using a mouse model of burn injury, our laboratory previously reported a requirement for CD1-restricted NKT cells in injury-induced immune suppression. To further explore the interactions between NKT cells and the cells that express CD1d molecules (i.e. dendritic cells (DCs)) we used an adoptive transfer approach to examine the effect of burn injury on the ability of DCs to regulate immunity in a CD1d-NKT celldependent manner. Briefly, wild-type (wt) BALB/c and BALB/c-CD1d ko mice were immunized with ovalbumin (OVA) and 7 days later, given a 15% total body surface area sham or dorsal scald injury. Twenty-four hours later, splenic DCs (≥95% CD11c+) were prepared from each group and transferred (1x106 cells per mouse, i.v.) to OVA-immunized, uninjured wt recipients, who were then examined 24 hours later for OVAspecific delayed type hypersensitivity (DTH) responses and IFNγ and IL-2 production by splenic T cells. Recipients of DCs from sham-injured mice displayed robust DTH and IFNγ and IL-2 production by T cells. In contrast, recipients of DCs from burn injured wt mice had 60% reduction of the OVA-DTH response and their T cells produced 70% less IFNγ compared to controls. Recipient IL-2 production was not affected by DC transfer. Interestingly, transfer of DCs from burn-injured CD1d ko mice did not suppress DTH or IFNγ production in recipient mice. We also observed that while DCs from burn-injured wt mice (i.e. CD1d+) could suppress T cell immunity (DTH, IFNγ, T cell proliferation) when transferred to uninjured wt recipients, DCs from burn-injured wt mice could not suppress T cell immunity when transferred to syngeneic NKT cell-deficient mice (Jα281ko). Together, our results show that DCs are critical for the suppression of T cell immunity after injury and can continue to do so even when they are removed from the immune microenvironment of the injured host. Moreover, our results confirm that the DCs must express CD1d on their surface and must interact with NKT cells in order to suppress immunity after injury. Supported by NIH R01-AI056108.