Differentiation stages of human natural killer cells in lymphoid tissues from fetal to adult life.

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Abstract
Virtually all human granular lymphocytes expressed the HNK[human natural killer]-1 differentiation antigen when examined in lymphoid compartments from adults, neonates and fetuses. The HNK-1+ cells were distinguishable into 3 subsets having distinct antigenic phenotypes: HNK+T3-M1-, HNK+T3+M1- and HNK+T3-M1+. Thus, > 70% of the HNK-1+ cells from 13-17 wk fetuses (< 0.2% of nucleated cells) lacked T cell antigens (e.g., T3, T8, T4 and T6) and the M1 myeloid antigen. Morphologically, the HNK+T3-M1- cells consisted of 3 different types: small granular lymphocytes (< 10% of HNK-1+ cells), agranular small lymphocytes with a narrow rim of cytoplasm (70-80%) and agranular giant cells (> 15 .mu.m) with considerable neutrophilic cytoplasm (15%). The purified fetal HNK-1+ cells exhibited a low level of cytotoxicity against human erythroleukemia K562 target cells. Almost all of HNK-1+ cells in neonatal tissues as well as adult bone marrow, lymph node and thymus exhibited the HNK+T3+M1-phenotype, contained sparse cytoplasmic granules and had an intermediate level of NK functional activity. Only adult blood and spleen contained a majority of mature HNK-1+ cells. These cells had an HNK+T3-M1+ phenotype, abundant cytoplasmic granules and maximum NK function. Evidently, HNK cells may generate from a separate cell lineage, and they may alter their phenotype, morphology and functional capability during differentiation.

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