COMMITMENT AND MAINTENANCE OF THE ALPHA-BETA AND GAMMA-DELTA T-CELL LINEAGES

We have generated transgenic mice using a rearranged, functional TCR-gamma gene that lacks the C gamma 1 3' silencer element, together with a TCR-delta cDNA construct designed for expression in lymphoid cells. All transgenic mice that descended from nine founders expressed alpha beta T cells and elevated levels of gamma delta T cells at various ratios. This observation does not support the proposal that alpha beta T cells are generated from T precursors in which C gamma 1 genes have been repressed via the cis-acting 3' silencer element, but it supports the idea that lineage commitment occurs independently of TCR gene expression. In seven transgenic lines, despite the absence of the 3' C gamma 1 silencer on the gamma transgene, the transgenic TCR is expressed only in gamma delta and not in alpha beta T cells. In the other two lines, in addition to T cells that express either the alpha beta or gamma delta TCR, a substantial fraction of T cells expresses both alpha beta and gamma delta TCR. These two lines also carry the highest number of copies of TCR-gamma transgene. However, in general, there is no correlation between the copy number of the gamma transgene and the fraction of T cells expressing the gamma delta TCR. The implications of these data are discussed.