The role of the thymic microenvironment in regulating events that occu
r subsequent to the acquisition of CD4, CD8, and the TCR, such as posi
tive and negative selection, has been studied extensively, However, co
mparatively less is known about how thymic stromal cells regulate grow
th and differentiation within the CD4(-)CD8(-)TCR(-) triple negative (
TN) cell compartment, Long-term culture systems have played a pivotal
role in the understanding of microenvironmental regulation of myelopoi
esis and B lymphopoiesis, but establishment of comparable cultures for
T lineage cells has proved challenging, This report describes a cultu
re system in which a thymic stromal cell line preferentially supports
the long-term growth of TN thymocytes, In addition to demonstrating th
at TN cells have a considerable proliferative potential, the results p
rovide insights into the effects of IL-7 on the growth and/or survival
of TN cells and its role in regulating TCR gene rearrangements, The a
bility of the cultured TN cells to mature into CD4- and/or CD8-express
ing thymocytes, some of which express TCR-alpha beta, suggests that th
e system will be valuable for the identification of microenvironmental
stimuli that regulate the maturation of TN cells.