Shen F, Xu X L, Graf L H, Chong A S
Department of General Surgery, Rush Presbyterian St. Luke's Medical Center, Chicago, IL 60612.
J Immunol. 1995 Jan 15;154(2):644-52.
The in vitro demonstration of the ability of NK cells to secrete cytokines prompted in vivo studies that illustrated the importance of NK cell-derived cytokines in regulating immune responses. Cross-linking of CD16 on NK cells can stimulate cytokine production. CD16-independent interactions capable of stimulating cytokine production have also been described, but molecules mediating such stimulations remain to be biochemically defined. We report here that cross-linking of CD45 specifically stimulates IFN-gamma production in human NK cells. The NK cells used 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 dependent on CD16, as CD45 mAbs of both IgG1 and IgG2a isotypes were equally 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 specific for CD45RO, but not CD45RA, were able to stimulate IFN-gamma production in NK cells. It has been reported that one ligand for CD45RO is 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 CD45RO Abs. In addition, neither of the CD22-transfectants were able to stimulate NK3.3 cells to secrete IFN-gamma. These observations collectively suggest that binding of NK3.3 cells to CD22 may be independent of CD45RO on NK3.3 cells.
自然杀伤（NK）细胞分泌细胞因子能力的体外实验结果推动了体内研究，这些研究阐明了NK细胞衍生的细胞因子在调节免疫反应中的重要性。NK细胞上CD16的交联可刺激细胞因子的产生。也有报道称存在不依赖CD16的能够刺激细胞因子产生的相互作用，但介导此类刺激的分子仍有待进行生化鉴定。我们在此报告，CD45的交联可特异性刺激人NK细胞产生γ干扰素。所用的NK细胞为经白细胞介素-2激活的贴壁NK细胞以及NK3.3细胞系。CD45单克隆抗体刺激NK细胞的能力似乎不依赖于CD16，因为IgG1和IgG2a两种亚型的CD45单克隆抗体具有同等的刺激作用，与完整的抗CD45单克隆抗体相比，F(ab')2片段也具有同等刺激作用。静息NK细胞与T细胞一样，主要表达CD45RA，而经白细胞介素-2激活的贴壁NK细胞会获得CD45RO的表达。特异性针对CD45RO而非CD45RA的抗体能够刺激NK细胞产生γ干扰素。据报道，CD45RO的一种配体是CD22β。我们测试了表达CD22的转染细胞与NK细胞结合并刺激NK细胞的能力。虽然NK细胞可与CD22α和CD22β转染细胞结合，但这种相互作用不受CD45RO抗体的抑制。此外，两种CD22转染细胞均无法刺激NK3.3细胞分泌γ干扰素。这些观察结果共同表明，NK3.3细胞与CD22的结合可能不依赖于NK3.3细胞上的CD45RO。
