El copyright pertenece a The Rockefeller University PressHematopoietic cells present in the liver in early human fetal life were characterized by phenotypic analysis using a broad panel of monoclonal antibodies. Expression of very late antigen 4 and leukocyte function-associated antigen 3 cell adhesion receptors and 4F2 cell activation molecules was found in all fetal liver hematopoietic cells before acquisition of T cell-, B cell-, or myeloidspecific surface markers, and before the time ofintrathymic colonization. Molecular studies showed that expression of the interleukin 2 receptor [beta] (IL-2R[Beta]) also occurred in the embryonic liver at this early ontogenic stage. In contrast, no expression of IL-2R[alfa] or IL-2 transcripts was found in fetal liver cells, whereas transcription of the IL-4 gene was detected in a small fetal liver cell subset. Putative T cell precursors were identified among the hematopoietic fetal liver cells by the expression of genes encoding the [gamma,delta,epsilon] and [zera] invariant chains of the CD3-T cell receptor (TCR) complex. However, no transcription of the polymorphic [alfa] and [beta] TCR genes was detected. Functional in vitro assays further demonstrated that fetal liver hematopoietic cells from those early embryos were capable of proliferating in response to T cell growth factors, including IL-4 and IL-2. However, whereas IL-4-induced proliferation paralleled the appearance in vitro of CD45+CD7-CD4 'hm cells expressing the CD14 myeloid antigen, as well as of CD34 + primitive hematopoietic progenitors, differentiation into CD45 + CD7 + CD8 + CD3- immature T cells was observed when using II.-2. Moreover, coculture with thymic epithelial cell monolayers provided additional evidence that early fetal liver hematopoietic cells may include very primitive T cell precursors, which were able to differentiate in vitro into TCR [alfa/beta] + mature T cells. Therefore, our results indicate that, after triggering of the T cell-specific maturation program in primitive fetal liver hematopoietic progenitors, specific signals provided intrathymically by epithelial cells may fulfill the requirements to drive terminal differentiation of prethymically committed T cell precursors.Peer reviewed