Unlike mature myeloid and monocytic cells and cell lines committed to terminal myelomonocytic differentiation, highly purified preparations of human natural killer cells/large granular lymphocytes (NK/LGL) did not spontaneously express the c-fos proto-oncogene. Transient expression of c-fos in NK/LGL was associated with functional activation with IL-2, IFN-gamma, LPS and PMA, which increased their cytotoxic activity, lymphokine secretion and in vitro chemotaxis. These results, together with the finding that T-cell receptor genes are in germ-line configuration in the vast majority of peripheral blood NK/LGL, are compatible with the hypothesis that these cells represent a separate hematopoietic lineage.
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