CD45-NEGATIVE MUTANTS OF A RAT NATURAL-KILLER-CELL LINE FAIL TO LYSE TUMOR TARGET-CELLS

To examine the role of CD45 in NK cell activation, we isolated three m utants and one variant of a rat NK cell line, RNK-1 6. Each of these l acked cell-surface expression of CD45 and did not have detectable tran scripts for CD45 on Northern blot analysis. The CD45-negative cells ex pressed CD2, CD53, and NKR-P1, but mAb-induced perturbations of these molecules did not induce protein tyrosine phosphorylations and increas es in the concentration of cytoplasmic-free calcium, as occurred in th e wild-type RNK-1 6. Unlike the wild-type cells, the CD45-negative cel ls failed to lyse YAC-1 and RL-male-1 tumor targets. The cytolytic act ivity of the CD45-negative cells could be stimulated pharmacologically by ionomycin and PMA, which, when added to the cytotoxicity assays, i nduced killing of tumor targets. These studies suggest that CD45 is re quired for the response of RNK-16 cells to target cells and for signal ing through CD2, CD53, and NKR-P1.