Adult human hepatocytes promote CD4+ T cell hyporesponsiveness via interleukin-10 producing allogeneic dendritic cells
(2014) Cell Transplantation — Vol. 23, n° 9, p. 1127-1142 (2014)
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- Abstract
- The success of liver cell therapy remains closely dependent on how the infused cells can beaccepted after transplantation, which is directly related to their degree of immunogenicity. Inthis study, we investigated the in vitro immunogenic properties of isolated human hepatocytes(hHeps) and adult derived human liver progenitor cells (ADHLPCs), an alternative cellcandidate for LCT. The constitutive expression of immune markers was first analyzed onthese liver-derived cells by flow cytometry. Human liver-derived cells were then coculturedwith allogeneic human adult peripheral blood mononuclear cells (PBMCs) and the resultingactivation and proliferation of PBMCs were evaluated, as well as the cytokine levels in thecoculture supernatant. The effect of liver-derived cells on dendritic cells (DCs) properties wasfurther analyzed in a secondary coculture with naive CD4+ T cells. We report that hHeps andADHLPCs expressed human leukocyte antigen (HLA) class I and Fas but did not expressHLA-DR, Fas ligand and costimulatory molecules. hHeps and ADHLPCs did not induce Tcell activation or proliferation. Moreover, hHeps induced a cell contact-dependent productionof interleukin (IL)-10 that was not observed with ADHLPCs. The IL-10 was produced by amyeloid DC subset characterized by an incomplete mature state. Furthermore, hHep-primedDC induced an antigen-independent hyporesponsiveness of naive CD4+ T lymphocytes thatwas partially reversed by blocking IL-10, whereas DC previously cultured alone did not.CONCLUSION: hHeps and ADHLPCs present a low immunogenic phenotype in vitro. AllogeneichHep but not ADHLPC promote a cell contact-dependent production of IL-10 by myeloidDCs, which induces naive CD4+ T cells antigen-independent hyporesponsiveness.
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Sana, G., Lombard, C., Vosters, O., Jazouli, N., André, F., Stéphenne, X., Smets, F., Najimi, M., & Sokal, E. (2014). Adult human hepatocytes promote CD4+ T cell hyporesponsiveness via interleukin-10 producing allogeneic dendritic cells. Cell Transplantation, 23(9), 1127-1142. https://doi.org/10.3727/096368913X666421 (Original work published 2014)