Role of CD44 in the development of natural killer cells from precursors in long-term cultures of mouse bone marrow
Delfino, D.V.; Patrene, K.D.; DeLeo, A.B.; DeLeo, R.; Herberman, R.B.; Boggs, S.S.
Journal of Immunology 152(11): 5171-5179
1994
ISSN/ISBN: 0022-1767 PMID: 7514628 Document Number: 423872
The role of the adhesion molecule CD44 in the development of NK cells was analyzed in a mouse long-term bone marrow culture system. After 4 wk of culture (day 0), recombinant human IL-2 was added and 13 days later the cells generated were shown to have substantial cytotoxic activity against YAC-1 and to be enriched for NK cells, as assessed for NK-1 .1 phenotype by flow cytometric analysis. Physical separation between stroma and precursors partially inhibited proliferation and, consequently, a lower number of cytotoxic cells were produced. Similar results were obtained when an anti-CD44 mAb was added together with IL-2 at day 0. The disruption of hyaluronic acid (HA), one of the ligands of CD44, by hyaluronidase or the competition for the binding of CD44 by soluble HA added with IL-2 on day 0 inhibited both proliferation and development of cytotoxicity to a greater degree than did anti-CD44. These results indicate that interaction of CD44 with HA plays an important role in the development of pre-NK cells into cytotoxic effector cells.