Distal Lck Promoter–Driven Cre Shows Cell Type–Specific Function in Innate-like T Cells

Innate-like T cells, including invariant NKT cells, mucosal-associated invariant T (MAIT) cells, and γ δ T (γδT) cells, are groups of unconventional T lymphocytes. They play important roles in the immune system. Because of the lack of Cre recombinase lines that are specific for innate-like T cells, pan–T cell Cre lines are often used to study innate-like T cells. In this study, we found that distal Lck promoter–driven Cre (dLckCre) in which the distal Lck gene promoter drives Cre expression in the late stage of thymocyte development has limited function in the innate-like T cells using ROSA26(floxed-Stop-tdTomato) reporter. Innate-like T cells differentiate into mature functional subsets comparable to the CD4(+) Th subsets under homeostatic conditions. We further showed that dLckCre-expressing γδT cells are strongly biased toward γδT1 phenotype. Interestingly, the γδT cells residing in the epidermis and comprising the vast majority of dendritic epidermal T cells nearly all express dLckCre, indicating dLckCre is a useful tool for studying dendritic epidermal T cells. Taken together, these data suggest that Lck distal promoter has different activity in the conventional and unconventional T cells. The use of dLCKcre transgenic mice in the innate-like T cells needs to be guided by a reporter for the dLckCre function.