Author/Editor     Radošević-Stašić, Biserka; Markovčič-Šutić, Ines; Šimin, Marija; Rukavina, Daniel
Title     Antitumor efficancy of intrahepatic natural killer T cell in animal models
Translated title     Protitumorska učinkovitost intrahepatičnih naravnih celic ubijalk T pri živalih
Type     članek
Source     Med Razgl
Vol. and No.     Letnik 43, št. Suppl 5
Publication year     2004
Volume     str. 159-65
Language     eng
Abstract     Natural killer T (NKT) cells, which co-express the invariant T cell receptor and markers of NK cells lineage (NK1.1 and IL-2Rbeta) have hecome 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.
Summary     Naravne celice ubijalke T (NKT), ki izražajo invariantni T-celični receptor in označevalce celične vrste NK (NK1.1 in IL-2Rbeta), so v zadnjih letih postale pomemben predmet raziskovanja, saj so očitno povezane z naravno odpornostjo za tumorje, nekatere povzročitelje okužb in za nastanek avtoimunosti. Kako te celice delujejo, še ni znano. Ve pa se že, da je njihovo delovanje omejeno s CD1, saj se vežejo z glikolipidnimi ligandi, proteini vročinskega šoka in dugimi dejavniki, povezanimi s stresom. Verjetno je, da so pomembne za spoznavo in prenos informacij, ki nastanejo ob nastanku tumorjev ali pa ob poškodbi telesnih celic. Posredno lahko sprožijo dejavnost imunskega sistema ali neposredno zavrejo tumorsko rast. Nadalje lahko izdelujejo različne citokine, ki vplivajo na ravnovesje med celicami TH1 in TH2. Celice NKT zelo verjetno nastajajo tudi zunaj priželjca, najverjetneje v jetrih. V naši raziskavi smo ugotovili, da pri miših nastanek jetrnih celic NKT sprožijo: a) delna hepatektomija (pHx), b) vbrizganje streptozotocina (sredstvo, ki izzove nastanek avtoimunskega diabetesa) in c) vbrizganje peptidoglycan monomera - PGM in PGM-Zn, ki ju pripravljamo iz po Gramu pozitivnih bakterij. V navedenih poskusih smo ugotovili, da so pravkar osamljene MNLC iz jeter in vranice za celice YAC-1 in singenske timocite močno ubijalske, kar spodbuja domnevo, da so avtoreaktivne jetrne celice NKT zelo pomembne pri uravnavanju protitumorske imunosti in za razmnoževanje epitelijskih celic.
Descriptors     KILLER CELLS, NATURAL
ANTINEOPLASTIC AGENTS
NEOPLASMS
MICE, INBRED CBA
DISEASE MODELS, ANIMAL
HEPATECTOMY
DIABETES MELLITUS, EXPERIMENTAL
FLOW CYTOMETRY