Prolonged IFN-γ-producing NKT response induced with α-galactosylceramide-loaded DCs

Natural killer T (NKT) lymphocytes mediate a rapid reaction to the glycolipid drug galactosylceramide (alphaGalCer), which triggers release of large amounts of cytokines into the serum within 12 h, starting with interleukin 4 (IL-4). When alphaGalCer is administered to mice on dendritic cells (DCs) instead, the response is more prolonged (> 4 days) and marked by a large expansion in IFN-gamma-producing NKT cells as well as greater resistance to metastases of the B16 melanoma. Nevertheless, DCs from mice given free alphaGalCer are able to induce strong IFN-gamma-producing NKT responses when transferred to naive mice, but not when transferred to alphaGalCer-treated recipients. In the latter, the NKT cells are anergized and can respond to glycolipid only in the presence of supplemental IL-2.Therefore, when alphaGalCer is selectively targeted to DCs, mice develop a stronger, more prolonged and effector type of NKT response, but this response can be blocked by the induction of anergy after presentation of alphaGalCer on other cells.