Naslov
Liver regeneration in MHC class I deficient and NK1.1. depleted mice

Autori
Radošević-Stašić, Biserka ; Trobonjača, Zlatko ; Ćuk, Mira ; Ravlić-Gulan, Jagoda ; Mrakovčić-Šutić, Ines ; Rukavina, Daniel

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

Izvornik
Immunology Letters (Abstract Issue) 56 (1997), 1-3 / Wagner, H. ; Heeg, K. ; Pfeffer, K. - Amsterdam : Elsevier, 1997, 245-245

Skup
13th Europen Immunology Meeting

Mjesto i datum
Amsterdam, Nizozemska, 22.06.1997. - 25.06.1997

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
liver regeneration; MHC deficient mice; NK.1.1. cells

Sažetak
Introduction: Liver regeneration that follows after partial hepatectomy (pHx) is well defined process which involves the concerted action of extra and intracellular factors resulting in induction of cell replication and its inhibition at time when the entire liver mass is restored. Since it has been implicated that partial resection of parenchyma organs may lead to the breakdown of previously maintained tolerance to self antigens and activation of pre-immune or natural immune repertoire in this study we attempted to analyse the role of major histocompatibility antigens (MHC) class I-encoded molecules and natural killer (NK) cells is these events. Material and methods: For this purpose C57Bl/6 mice which were homozygous or heterozygous for b2 microglobulin (b2-m) deficiency were used. They do not express correctly folded MHC class I trimolecular complexes and are devoid of CD8+ T cells. Liver regeneration was provoked by 1/3 pHx. Phenotype of locally activated lymphoid cells and intensity of liver growth after pHx were estimated by cytofluorometric screening of intrahepatic lymphoid cells and cell cycle analysis, respectively. In additional experiments the consequences of in vivo depletion of NK1.1+. cells on liver regeneration and on thymic cell cycle and differentiation were done. Results: The data have shown that in homozygous b2-m -/- mice the S phase of hepatocytes in the regenerating liver is initially reduced (at 24th hour) and then markedly increased (at 48 h and 7 days pHx) in comparison to their heterozygous littermates. In both groups an early peak of intrahepatic NK1.1.+ and CD5+ cells was seen, disappearing on the second p.o.day. Depletion of NK1.1.+ cells, however, only in b2-m +/- augmented the S phase of hepatocytes (1st and 2nd day after pHx). Simultaneously, a significant decline of CD5+, CD8+, CD5+ CD8+ cells, TCRab+ and Vb8+ intrahepatic cells was found in b2-m +/- mice , while in b2-m -/- mice an initial increase of CD5+, CD3+, Vb6+ and Vb8+ and TJ-6+ cells was seen. Enhancing effect on hepatocytes was only in MHC Class I expressing mice followed by an anti NK1.1. insensitive decline of CD4+CD8+ T cells in thymus (at 2nd day) , which was followed by augmented proportion of cells bearing the apoptotic marker TJ6 . Conclusions: The data point to the activation of extrathymic T cells differentiation in the regenerating liver and to MHC class I depended regulation of lytic activity of various type of intrahepatic NK cells. Additionally the results imply that self-reactive lymphocytes activated by pHx may be eliminated in thymus by processes of negative selection.

Izvorni jezik
Engleski

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