Proximal Lck Promoter-Driven Cre Function Is Limited in Neonatal and Ineffective in Adult γδ T Cell Development

During T cell development, Lck gene expression is temporally controlled by its proximal and distal promoters. The pLckCre transgenic mouse available from The Jackson Laboratory, in which the proximal promoter of Lck drives Cre expression, is a commonly used Cre driver line to recombine genes flanked by loxP sites in T cells. pLckCre drives recombination early in thymocyte development and is frequently used to delete genes in alpha beta and gamma delta T cells. We found that pLckCre failed to efficiently delete floxed genes in gamma delta T cells in contrast to a complete deletion in conventional as well as unconventional alpha beta T cells. Mechanistically, gamma delta T cells inefficiently transcribed the endogenous proximal Lck promoter compared with alpha beta T cells during adult thymic development. A small population of gamma delta T cells that had activated pLckCre was detected, many of which were located in nonlymphoid organs as well as precommitted IL-17- or IFN-gamma-producing gamma delta T effector cells. In newborn thymi, both pLckCre and endogenous Lck proximal promoter expression were substantially enhanced, giving rise to an elevated fraction of gamma delta T cells with recombined floxed genes that were increased in unique gamma delta T subsets, such as the IL-17-producing gamma delta T cells. Our data point out striking differences in Lck transcription between perinatal and adult gamma delta T cell development. Taken together, the data presented in this study shed new light on gamma delta T cell development and stimulate a reanalysis of data generated using the pLckCre transgenic mice.