Scientists here have made a major discovery that sheds new light upon the growth and development of human natural killer (NK) cells, powerful but somewhat mysterious components of the body’s immune system that are the first line of defense against cancer and infectious diseases.
Scientists have believed for years that human NK cells are generated in bone marrow, but Michael Caligiuri, director of the OSU Comprehensive Cancer Center and the senior author of the study, says research in his laboratory shows that the precursors to NK cells are actually found in cellular nurseries deep inside the body’s lymph nodes.
The findings, appearing in the Mar. 22 issue of the journal Immunity, may offer clinicians new direction in determining how to manipulate this cell type in enhancing immune responses to cancer.
“This study is fundamentally about understanding the immune system more fully so we can help patients,” says Caligiuri.
A major arm of the body’s defense system is made up of lymphocytes, cells that fall broadly into three categories – T cells, B cells and NK cells.
Although all lymphocytes stem from a common source – progenitor cells in the bone marrow – they take different paths in developing into full-fighters in the immune system. For example, cells destined to become T cells, sophisticated and highly focused killer cells, are released into the bloodstream and migrate to the thymus where they learn their role. In contrast, B cells, which make antibodies, remain and mature in the bone marrow. Until now, scientists thought NK cells did the same.
But Caligiuri, working with Aharon Freud, the lead author of the study and a doctoral candidate in Caligiuri’s laboratory, had noted other work showing that mice lacking lymph nodes also lacked NK cells. In addition, in earlier research in Caligiuri’s laboratory, scientists had identified two distinct subsets of human NK cells (referred to as CD56 bright and CD56 dim cells) and they observed that the bright subset appeared much more frequently in lymph nodes than in bone marrow or circulating blood.
In other words, they had a hunch traditional thinking about the origin of human NK cells might be wrong.
In building a case to support their beliefs, they first identified the NK precursor cell, then, they measured the number of the precursors in different parts of the body. Through flow cytometry, they discovered that while NK precursors make up about 1 percent of bone marrow progenitor cells and 6 percent of circulating blood progenitor cells, they comprise virtually all of the progenitor cells found in lymph nodes.
Interestingly, Gerard Nuovo, a pathologist and co-author of the study, discovered that these novel NK precursor cells are not randomly strewn throughout the lymph nodes, but rather localized near special sites called parafollicular regions, rich in T cells and NK bright cells.