IDENTIFICATION AND PARTIAL-PURIFICATION OF A HUMAN NATURAL-KILLER-CELL PROLIFERATION-INDUCING FACTOR

Culture supernatants of Concanavalin A activated human peripheral bloo d mononuclear cells were found to contain a factor which induced proli ferative response in normal peripheral blood mononuclear cells. This p roliferation-inducing factor specifically induced and sustained prolif eration of purified human NK cells but not of T or B cells. Although i nterleukin 2 (IL2) also has proliferation-inducing effects on NK cells , the partially purified proliferation-inducing factor preparations co ntained no measurable IL2 contamination, Moreover, neutralizing anti-I L2 antibodies did not block the growth effect of proliferation-inducin g factor on purified human NK cells. Other cytokines which were tested , including IL4, IL6, IL7, IL12, TNF and IFN, were all found to be ina ctive in the proliferation-inducing factor assay. While proliferation- inducing factor by itself had no effect on T-cell proliferation, IL2-i nduced proliferation of T cells was significantly enhanced in the pres ence of proliferation-inducing factor, as was IL2-induced NK-cell prol iferation. NK cells could be maintained in culture for at least a mont h in the presence of proliferation-inducing factor alone, but the cell s lost their cytolytic activity after 3-4 weeks in culture. Addition o f IL2, to NK cells which had been cultured in the presence of prolifer ation-inducing factor, restored their cytotoxicity, Proliferation-indu cing factor activity was partially purified on an anion exchange HPLC column. The molecular weight of proliferation-inducing factor appeared to be about 10 kDa, based on its elution profile on a sizing HPLC col umn. Our results indicate that proliferation-inducing factor is a nove l NK-cell proliferation-inducing factor.