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Characterization of Thymic Settling Progenitors in the Mouse Embryo Using In Vivo and In Vitro Assays
Published on: June 9, 2015
Unique progenitors in mouse lymph node develop into CD127+ NK cells: thymus-dependent and thymus-independent pathways
Claudia Luther1, Kathrin Warner, Fumio Takei
1Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC.
Blood
|March 1, 2011
Summary
The origin of CD127(+) natural killer (NK) cells in mouse lymph nodes (LNs) is clarified. Unique NK cell progenitors (NKPs) in LNs can generate these CD127(+) NK cells, independent of the thymus.
Area of Science:
- Immunology
- Cell Biology
Background:
- A subset of natural killer (NK) cells expressing CD127 (IL-7 receptor-α chain) resides in mouse lymph nodes (LNs).
- Their thymic origin is questioned due to their presence in athymic mice, leaving their source unclear.
Purpose of the Study:
- To identify and characterize the origin of CD127(+) NK cells within the mouse lymph node.
- To investigate the potential of identified progenitors to generate functional CD127(+) NK cells.
Main Methods:
- Identification of unique NK cell progenitors (NKPs) in mouse LNs based on surface markers (CD49b, CD127, CD122, lineage markers).
- In vitro differentiation assays of identified NKPs.
- In vivo transplantation into lymphopenic mice.
- Subdivision of NKPs into stem cell antigen-1 (Sca-1)(hi) and Sca-1(lo) subsets for comparative analysis.
Main Results:
- Unique LN NKPs expressing CD49b and CD127 were identified.
- These LN NKPs differentiated into functional CD127(+) NK cells in vitro and in vivo.
- LN NKPs consist of Sca-1(hi) and Sca-1(lo) subsets, with distinct frequencies in normal versus athymic mice.
- Sca-1(lo) NKPs, but not Sca-1(hi) NKPs, generated CD127(+) NK cells with rearranged TCRγ genes.
Conclusions:
- CD127(+) NK cells in mouse LNs originate from both thymus-dependent (Sca-1(lo)) and thymus-independent (Sca-1(hi)) LN NKPs.
- These findings resolve the ambiguity surrounding the origin of CD127(+) NK cells in the LN.
- Identified LN NKPs represent a crucial source of these immune cells, contributing to both innate and adaptive immune responses.
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