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

Abstract

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-1hi and Sca-1lo NKPs develop into CD127+ NK cells in vitro, only those derived from Sca-1lo 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-1lo and thymus-independent Sca-1hi LN NKPs. © 2011 by The American Society of Hematology.