engleski

Regulatory role of intrahepatic natural killer T cells in liver regeneration

Recent discoveries have focused attention on nonclassical MHC class I molecules, as well as on the development and function of a subset of primitive T lymphocytes, which express a highly restricted T cell receptor (TCR) repertoire as well as classical NK receptors. These NKT cells recognize particular types of foreign antigens, such as micro bacterial antigens or synthetic hydrophobic peptides, presented by CD1-molecules. Many of CD1-restricted T cells, however, appear also to be autoreactive cells, capable to react on various self-antigens, released from various cell compartments. Although, these characteristics suggest that CD1-restricted NKT cells might be involved in the regulation of tissue healing after quotidian injures, the knowledge about their participation in normal growth is still the subject of speculation. Testing the potential role of autoreactive NKT clones in the control of liver regeneration after 1/3 partial hepatectomy (pHx), in this study we investigated the dynamics of liver regeneration in wild, MHC class I deficient, NKT-cell depleted and perforin knock out C57Bl/6 mice, determining the phenotype of intrahepatic and thymic lymphatic cells and correlating the findings with the changes in liver regeneration, estimated by cell cycle analysis of hepatocytes. The data have shown that in early phase of regeneration in the liver accumulate particularly NK1.1+ /CD3intermadiate cells, which co-express CD69, as well as CD8+, TCR a/b+, Vb8.1-8.2+ cells, and TCR g/d+ cells. Their proportion in the liver decreased after in vivo application of anti-NK.1.1 antibodies, suggesting that they were NKT cells, or that during the liver regeneration NKT were necessary for activation and proliferation of other T cells. In mice defective in b2-microglobulin this dynamics was completely changed, suggesting the involvement of CD1-molecules. Simultaneously made cycle analysis of hepatocytes in the remaining liver showed that mice with nonfunctional MHC-class I molecules and perforin-deficient mice in comparison with wild mice had initially smaller (on 1st day) and then greater (at 3rd and 7th day) fraction of cells in G2+M phase, suggesting that CD1-restricted NKT cells or MHC-class I restricted cytotoxic CD8 T lymphocytes had regulatory role in these events. Moreover, in NKT cells-depleted wild mice, the increased proportion of hepatic cells in S and G2+M phase was found in early phase of liver regeneration (at the 1st day after pHx). Taken together, the data point to the possibility that during regeneration in the remaining liver are activated autoreactive, b2-microglobulin associated NKT cells, which as cytotoxic cells, through perforin-dependent pathway control the intensity of reparatory process, killing probably the superfluous or altered self cells.

liver regeneration; NKT cells

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