engleski

Antitumor efficancy of intrahepatic natural killer T cells in animal models

Natural killer T (NKT) cells, which co-express the invariant T cell receptor and markers of NK cells lineage (NK1.1 and IL-2Rb) have become a major focus in the studies of the innate immune response to tumors and infectious diseases, as well as in autoimmunity, but the precise immunological function of these "primitive" T lymphocytes is still not well defined. As CD1-restricted cells they interact with glycolipid ligands, heat shock proteins and other "stress" or "danger" signals produced by tumors or injured self cells, transferring important information to the rest of the immune system or directly suppressing the tumor growth. Furthermore, depending on the stimulus they produce various immunomodulatory cytokines, affecting the TH1/TH2 immune balance. Since, particularly the liver might be a site of extrathymic generation of the NKT cells we demonstrate herein evidence that in mice these cells might be induced by: a) partial hepatectomy (pHx), b) injections of streptozotocin (provoking autoimmune diabetes) and c) injections of peptidoglycan-monomer-PGM and PGM-Zn, prepared from Gram + bacteria. The data also showed, that in all experimental models, freshly isolated hepatic and particularly splenic MNLC became markedly cytotoxic to YAC-1 cells, as well as to syngeneic thymocytes, suggesting that autoreactive NKT cells in the liver, might be key players in the regulation of anti-tumor immunity and epithelial cell proliferation.

Natural killer T cells; liver; partial hepatectomy; diabetes mellitus; peptidoglycan monomer

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