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 Blood, 15 April 2008, Vol. 111, No. 8, pp. 4201-4208.
Prepublished online as a Blood First Edition Paper on January 28, 2008; DOI 10.1182/blood-2007-04-087577.

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IMMUNOBIOLOGY

Unique subset of natural killer cells develops from progenitors in lymph node

Linnea L. Veinotte*,1,2, Timotheus Y. F. Halim*,1,2, and Fumio Takei1,3

1 Terry Fox Laboratory, British Columbia Cancer Agency; 2 Genetics Graduate Program and 3 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver

Natural killer (NK) cells have been thought to develop from committed progenitors in the bone marrow. However, a novel pathway of thymus-dependent NK-cell development that produces a unique subset of NK cells expressing CD127 has recently been reported. We now have identified 2 populations of NK progenitors, one in the thymus and the other in the lymph node (LN). Immature double-negative 2 (CD4–CD8–CD44+CD25+) thymocytes have potential to produce NK cells with rearranged T-cell receptor {gamma} genes (Tcr{gamma}+) in vitro. Tcr{gamma}+ NK cells are rare in spleen but relatively abundant in the thymus and LN. Approximately 20% of LN NK cells are Tcr{gamma}+, and they are found at similar levels in both CD127+ and CD127– subsets. Moreover, a subpopulation of LN cells resembling immature thymocytes differentiates into Tcr{gamma}+ NK cells in vitro and also repopulates the NK compartment in lymphopenic mice. Athymic mice lack the LN NK progenitors expressing CD127 as well as Tcr{gamma}+ NK cells. These results suggest that Tcr{gamma}+ NK cells may be generated from unique progenitors in the thymus as well as in the LN.


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