Staphylococcal enterotoxin B can activate NKT cells independent of Cd1d

Abstract

Staphylococcal enterotoxin B (SEB) is a superantigen that can activate 5 to 30% of the T cell population and unlike conventional antigens, it directly binds to the MHC Class II molecules and activates T cells with variable TCR β chain such as Vβ8. Such activation triggers massive cytokine release that leads to rash, fever, and can often lead to multi‐organ failure, coma and death. The precise role of NKT cells in the cytokine production and toxicity induced by SEB is not clear. In this study, we investigated the role of NKT cells following SEB immunization. We found that SEB administration in vivo triggered Vascular Leak Syndrome (VLS) in the lungs of wild‐type (WT) mice while it was significantly decreased in Cd1d−/−mice lacking NKT cells. This was reversed when WT spleenocytes were injected into the Cd1d−/−mice. Cd1d−/−mice also exhibited decreased cytokine production in response to SEB, particularly IL‐4. When bone marrow derived dendritic cells (DCs) from WT and Cd1d−/−mice were tested for their ability to activate NKT cells, we noted that DCs from Cd1d−/−mice were able to activate NKT cells. Together, our studies demonstrate that NKT cells can be directly activated independent of CD1d. Thus, the plethora of cytokines produced following SEB can also be attributed to initial NKT cell activation (Supported in part by NIH grants: AI053703, ES09098, AI058300, DA016545, HL058641 and P01AT003961).