Common lymphoid progenitor-independent pathways of innate and T lymphocyte development

All lymphocytes are thought to develop from a single population of committed lymphoid progenitors termed common lymphoid progenitors (CLPs). However, upstream progenitors termed lymphoid-primed multi-potent progenitors (LMPPs) are known to be more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s), suggesting alternative pathways of their development. Here, we have divided LMPPs into CD127- (LMPP-s) and CD127+ (LMPP+s) subsets and compared them with CLPs. Adult LMPP+s are the most efficient progenitors for T cells and ILCs in transplantation assays, and lineage tracking by the recombinase expression also suggests that most ILC2s and NK cells develop from LMPPs independent of CLPs. In the neonatal period CLPs are rare and, unlike prominent neonatal LMPP+s, incapable of differentiating into ILC2s and T cells while their development is highly active. These results suggest non-linear pathways of innate and T lymphocyte development from LMPP+s with limited CLP contributions.Medicine, Faculty ofGraduat