NATURAL-KILLER-CELL PROLIFERATION INDUCED BY ANTI-NK1.1 AND IL-2

NKR-P1 molecules are involved in natural killing of certain tumour tar gets. Indeed, the NK1.1 (NKR-P1C) molecule is the most specific serolo gical marker on murine NK cells in C57BL/6 mice. Previous studies of N KR-P1 have indicated that anti-NKR-P1 mAb induced NK cells to kill oth erwise insensitive targets, NK cell phosphoinositol turnover and Ca+flux but it was not previously known if all NK cells were activated. I n this study we report that immobilized anti-NK1.1 also specifically i nduced proliferation as measured by thymidine incorporation. The respo nse required low doses of IL-2 for a synergistic effect. Cells stimula ted with anti-NK1.1 + IL-2 displayed characteristic cytolytic activity against a NK-sensitive tumour target, YAC-1. However, anti-NK1.1-stim ulated cells displayed delayed proliferation kinetics, heterogeneity o f the expression of the very early antigen marker, CD69, and altered e xpression of the Ly-49 family members when compared to NK cells activa ted by high concentrations of IL-2. Taken together, these data demonst rate that immobilized anti-NK1.1 triggers only a subpopulation of NK c ells.