| First Author | Fiala GJ | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 2 | Pages | 569-579 |
| PubMed ID | 31167772 | Mgi Jnum | J:302830 |
| Mgi Id | MGI:6323679 | Doi | 10.4049/jimmunol.1701521 |
| Citation | Fiala GJ, et al. (2019) Proximal Lck Promoter-Driven Cre Function Is Limited in Neonatal and Ineffective in Adult gammadelta T Cell Development. J Immunol 203(2):569-579 |
| abstractText | 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 alphabeta and gammadelta T cells. We found that pLckCre failed to efficiently delete floxed genes in gammadelta T cells in contrast to a complete deletion in conventional as well as unconventional alphabeta T cells. Mechanistically, gammadelta T cells inefficiently transcribed the endogenous proximal Lck promoter compared with alphabeta T cells during adult thymic development. A small population of gammadelta 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 gammadelta T effector cells. In newborn thymi, both pLckCre and endogenous Lck proximal promoter expression were substantially enhanced, giving rise to an elevated fraction of gammadelta T cells with recombined floxed genes that were increased in unique gammadelta T subsets, such as the IL-17-producing gammadelta T cells. Our data point out striking differences in Lck transcription between perinatal and adult gammadelta T cell development. Taken together, the data presented in this study shed new light on gammadelta T cell development and stimulate a reanalysis of data generated using the pLckCre transgenic mice. |
