Human thymocyte development in mouse organ cultures

AG Fisher, L Larsson, LK Goff, DE Restall… - International …, 1990 - academic.oup.com
AG Fisher, L Larsson, LK Goff, DE Restall, L Happerfield, M Merkenschiager
International immunology, 1990academic.oup.com
A novel system to study human thymocyte development is described in which embryonic
mouse thymic rudiments are seeded with human precursor cells in vitro. In these cultures
human thymocytes proliferate extensively (> 20-fold increase in cell number) and mature, as
evidenced by the accumulation of double and single positive (CD4+ and/or CD8+) cells.
Data presented here suggest that the survival and ordered development of the mature
human thymocytes in chimeric thymuses is dependent on human stromal elements …
Abstract
A novel system to study human thymocyte development is described in which embryonic mouse thymic rudiments are seeded with human precursor cells in vitro. In these cultures human thymocytes proliferate extensively (>20-fold increase in cell number) and mature, as evidenced by the accumulation of double and single positive (CD4+ and/or CD8+) cells. Data presented here suggest that the survival and ordered development of the mature human thymocytes in chimeric thymuses is dependent on human stromal elements. Immature CD4-CD8- human thymocytes failed to colonize or minimally recolonized mouse thymic lobes unless provided with high density (> 1.077 g/ml) human thymic cell fractions. These fractions contain multicellular complexes of epithelial/nurse cells, thymocytes, and dendritic cells/macrophages which dramatically enhanced the recolonizing capacity of purified CD4−CD8− thymocytes. The chimeric organ culture system described here provides not only a new approach for studying human T cell ontogeny but also a direct means for the future dissection of stromal interactions necessary for successful transition of precursor cells (CD4−CD8−) to immature double positive (CD4+ CD8+) and mature single positive cells (CD4+ or CD8+) in the thymus.
Oxford University Press