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Front-line immune cells mature in four stages, study shows

o is a doctoral student in Caligiuri's laboratory. "The next step is to figure out why they develop in lymph tissue and whether patients with cancer have altered NK cell development."

Scientists have known for some time that cells with a protein called CD34 on their surface can give rise to NK cells. They also knew that mature NK cells lack CD34. But how and where the CD34-bearing cells became mature NK cells was not understood.

For this study, Caligiuri, Freud and their collaborators analyzed tissues from more than 50 tonsils and 30 lymph nodes from the OSUCCC Tissue Procurement Shared Resource and from the National Disease Research Interchange.

Through a series of experiments, they identified additional protein markers, particularly one called CD117, that suggested that NK cells mature in four discrete stages in these tissues.

Ironically, a clue came 10 years ago, when Caligiuri discovered CD117 on mature NK cells. "NK cells were the only immune cell to express CD117, and CD117 is a stem-cell marker, so that told us there was a bridge between stem cells and NK cells." Once we discovered where to look (in lymph tissue), it was just a matter of careful, diligent work."

The researchers also isolated cells of each stage and showed that under the proper conditions, stage-1 progenitor cells matured into stage-2 NK cells, and that these cells matured into stage-3 cells and stage-4 cells, with the hallmarks and cell-killing capacity of mature NK cells.

The researchers are now working to gain a detailed understanding of stage-2 and stage-3 NK cells, including precisely where they mature within tonsils and lymph nodes and whether they play a role in immune responses or are just going through the maturation process.


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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University
19-Apr-2006


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