Naslov
Peptidoglycan monomer linked with zinc as a modulator of hepatic NKT cells

Autori
Mrakovčić-Šutić, Ines ; Radošević-Stašić, Biserka ; Šimin, Marija ; Radić, Davor ; Rukavina, Daniel ;

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Frontiers in Autoimmunity: Fundamental aspects and clinical perspectives.Abstact book / . - Budimpešta : A NATO Advanced Study Institute, 2002

Skup
Frontiers in Autoimmunity: Fundamental aspects and clinical perspectives

Mjesto i datum
Keszthely, Mađarska, 08.09.2002. - 18.09.2002

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
autoimmune diabetes mellitus; peptidoglycan-monomer linked with zinc; liver; NKT cells

Sažetak
Current knowledge shows that conditions such as stress, infection, autoimmune disease, pregnancy, and etc. elevate the number and function of extrathymic T cells, which are generated mainly in the liver. Phenotypically they belong to primitive T cells that coexpress receptors of the NK lineage and have unique potential to rapidly secrete large amount of cytokines, of both TH1 and TH2 type. Similar to NK cells, NKT cells can "see" and kill target cells deficient in the expression of one or more MHC class I molecule, but through invariant TCR, they can recognize also a large array of various exogenous nonpeptidic antigens, as well as endogenous self-antigens, presented in the context of nonpolymorphic CD1 molecules. It was, therefore, proposed that they represent self-reactive forbidden clones, which in some conditions mediate cytotoxicity against altered self-cells, malignant and microbially infected cells. Moreover, some hypotheses predict that NKT cells in decidua, recognizing the fetal antigens in a monomorphic MHC-restricted manner, protect the mother from the invasion of fetal cells. Since it is know that NKT cells are especially abundant in the liver, in this study we attempted to investigate their function and regulatory mechanisms in two experimental models: streptozotocin-induced autoimmune diabetes mellitus and syngeneic pregnancy. In both models it was proposed that they, as autoreactive clones, might have protective, but also the destructive effects, indicating that the final outcome depends on the time and the intensity of their activation, as well as, on the presence of co-activation signals. Trying to elucidate the possibility that especially bacterial products may regulate the function of hepatic NKT cells, in this work we tested the possibility that regulatory effects in these events might have peptidoglycan monomer (PGM), originally obtained from Brevibacterium divaricatum, and its new analogue PGM linked with zinc (PGM-Zn). The data revealed that during the autoimmune diabetes and syngeneic pregnancy the proportion of hepatic NKT cells markedly increased (from 15% to 49,5% or 35%, respectively). Freshly isolated suspension of hepatic mononuclear lymphatic cells, containing TCRint, NK1.1+ and IL-2R+ cells showed increased spontaneous cytotoxicity against YAC-1 cell line, as well as suspension of splenocytes, which, contained greater proportion of CD8+ T cells. Cultivation with PGM-Zn, however, in both models, significantly increased the cytotoxicity of both effector against NK sensitive (YAC-1) and lymphokine activated (P-815) targets. Since PGM, like other products of Gram (+) bacteria is acting through the complex of CD14-LBP and Toll-like receptors, the data suggest that pattern-recognition receptors and Zn2+ contribute to innate recognition mechanisms, and interplay between the innate and adaptive immune system, performing important physiological function in some pathological and physiological conditions.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Farmacija

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