Unique progenitors in mouse lymph node develop into CD127+ NK cells: thymus-dependent and thymus-independent pathways.

A subset of natural killer (NK) cells in normal mouse lymph node (LN) expresses CD127 (IL-7 receptor-α chain) and is thought to derive from the thymus. However, CD127(+) NK cells are found in the LN of athymic mice. Therefore, the origin of CD127(+) NK cells in the LN is unclear. Here, we have identified unique NK-cell progenitors (NKPs) in the LN that express the pan-NK cell marker CD49b and CD127 but lack CD122 and lineage markers. The LN NKPs develop in vitro into CD127(+) NK cells that display natural cytotoxicity and cytokine production capacity. They also become CD127(+) NK cells in lymphopenic mice that received a transplant. LN NKPs can be divided into stem cell antigen-1 (Sca-1)(hi) and Sca-1(lo) subsets. The latter comprise ∼ 60% of LN NKPs in normal mouse and < 10% of athymic mouse LN NKPs. Whereas both Sca-1(hi) and Sca-1(lo) NKPs develop into CD127(+) NK cells in vitro, only those derived from Sca-1(lo) LN NKPs have rearranged TCRγ genes. Thus, CD127(+) NK cells in the LN seem to be generated, at least in part, from both thymus-dependent Sca-1(lo) and thymus-independent Sca-1(hi) LN NKPs.