Thymosin-alpha(1) stimulates maturation of CD34(+) stem cells into CD3(+)4(+) cells in an in vitro thymic epithelia organ coculture model

The effect of thymosin-alpha(1) on thymopoiesis is largely unknown. Thymosi n is found in the cortical and medullary thymic epithelia, as well as in nu rse cells; thus, it is hypothesized that thymosin may affect both early and late stage of thymocyte maturation, In this study, the effect of thymosin- alpha(1) on thymopoiesis was determined by coculturing in vitro CD34(+) ste m cells (SC) with allogeneic cultured thymic epithelia fragments (CTEF) for 1-4 weeks and analyzing T-cell maturation by flow cytometry. Thymosin-alpha(1) significantly enhanced the cell number (e.g., proliferati on) of mononuclear cells obtained at 2 and 4 weeks of the SC-CTEF coculture s (P < 0.01 and < 0.05, respectively). In particular, thymosin-alpha(1) sti mulated expression of CD3(+) cells at 3 and 4 weeks (P < 0.05). The predomi nant subpopulation increased by thymosin stimulation was single positive ma ture CD4(+) cells, which was confirmed to occur within the SC-CTEF thymic o rgan tissue by laser confocal immunofluorescence microscopy. Thymosin stimu lation tended to enhance IL-7 synthesis, critical cytokine in the maturatio n of thymocytes. In summary, this is the first study to demonstrate that thymosin-alpha(1) e nhanced thymopoiesis of CD34(+) stem cells in humans using an in vitro mode l of differentiation using stem cells and cultured thymic epithelial fragme nts cocultures. Furthermore, the thymosin significantly increased expressio n of CD3(+)4(+) T cells. (C) 1999 International Society for Immunopharmacol ogy. Published by Elsevier Science Ltd.