CD45-CROSS-LINKING STIMULATES IFN-GAMMA PRODUCTION IN NK CELLS

The in vitro demonstration of the ability of NK cells to secrete cytok ines prompted in vivo studies that illustrated the importance of NK ce ll-derived cytokines in regulating immune responses. Cross-linking of CD16 on NK cells can stimulate cytokine production. CD16-independent i nteractions capable of stimulating cytokine production have also been described, but molecules mediating such stimulations remain to be bioc hemically defined. We report here that cross-linking of CD45 specifica lly stimulates IFN-gamma production in human NK cells. The NK cells us ed were IL-2-activated adherent NK cells and from the NK3.3 cell line. The ability of CD45 mAbs to stimulate NK cells appears not to be depe ndent an CD16, as CD45 mAbs of both IgG1 and IgG2a isotypes were equal ly stimulatory, as were F(ab')(2) compared with whole anti-CD45 mAbs. Resting NK cells, like T cells, express predominantly CD45RA, whereas IL-2 activated adherent NK cells acquire expression of CD45RO. Abs spe cific for CD45RO, but not CD45RA, were able to stimulate lFN-gamma pro duction in NK cells. It has been reported that one ligand for CD45RO i s CD22 beta. We tested the ability of CD22-expressing transfectants to bind to and stimulate NK cells. Whereas NK cells bound to CD22 alpha and CD22 beta transfectants, this interaction was not inhibited by CD4 5RO Abs. In addition, neither of the CD22-transfectants were able to s timulate NK3.3 cells to secrete IFN-gamma. These observations collecti vely suggest that binding of NK3.3 cells to CD22 may be independent of CD45RO on NK3.3 cells.