Extrathymic differentiation of T lymphocytes and natural killer cells from human embryonic liver precursors

Alessandro Poggi, Massimo Sargiacomo, Roberto Biassoni, Nicoletta Pella, Simona Sivori, Valentino Revello, Paola Costa, Mauro Valtieri, Giovanni Russo, Maria Cristina Mingari, Cesare Peschle, Lorenzo Moretta

Research output: Contribution to journalArticle

Abstract

Liver cells were isolated on Ficoll/Hypaque gradients from embryos or fetuses at 6-10 weeks of gestation; 2-20% of the cells expressed CD45 or HLA class I surface antigens and 2-6% expressed CD7. Other T- or natural-killer (NK)-cell-lineage-speciflc markers were undetectable. Liver-cell suspensions cultured in the presence of phytohemagglutinin and recombinant interleukin 2 gave rise to large proportions of CD3+ lymphocytes expressing either α/β or γ/δ T-cell receptors. This occurred not only in bulk cultures but also when cells were cloned under limiting dilution conditions. Importantly, these figures were obtained also in embryos at 6-8 weeks of gestation, which is before colonization of the thymic rudiment by T-cell precursors. When the same liver-cell suspensions were cultured in the presence of irradiated H9 cells and recombinant interleukin 2 (either in bulk cultures or under cloning conditions), large proportions of cells (or clones) expressed surface CD16 and CD56 antigens and displayed a strong cytolytic activity against both NK-sensitive (K562) and NK-resistant (M14) target cells. In addition, liver-derived T or NK cells expressed functional receptor molecules since they could be activated via either CD3/T-cell receptor or CD16 surface antigens, respectively. Further fractionation of liver cells on the basis of CD45 antigen expression indicated that only CD45+ cells could give rise to T or NK cells in culture. Thus, CD45 can be used as a marker for identification of an early liver-cell population containing T- and NK-cell precursors. That T or NK cells were derived from male embryos and not from the mother was shown by PCR amplification of X and Y chromosomal sequences. Our present data may offer an in vitro model for extrathymic embryonic T-cell maturation that can be used to examine fundamental aspects of human T-cell development and function.

Original languageEnglish
Pages (from-to)4465-4469
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number10
Publication statusPublished - May 15 1993

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ASJC Scopus subject areas

  • General
  • Genetics

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