Tan P H, Santos E B, Rossbach H C, Sandmaier B M
Transplantation Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
J Immunol. 1993 Feb 1;150(3):812-20.
In this study, we examined the in vitro effect of an anti-CD44 mAb, S5, on NK function using canine PBMC as effectors. S5 enhanced NK activity in a dose-dependent and rapid fashion as did IM7, another anti-CD44 mAb that recognizes a common epitope(s) on CD44. Other anti-CD44 mAb (Hermes-1 and S3) that recognize epitopes distinct from S5 and IM7 had a variable effect on NK activity. The activation of increased killing by S5 only occurred when NK-sensitive targets were used, suggesting that lymphokine-activated killer cells were not being induced. Antibody-dependent cell cytotoxicity was not the mechanism involved in the augmentation of NK activity, nor was it Fc receptor-dependent, inasmuch as S5 F(ab')2 was able to increase NK activity. F(ab') fragments of S5 were equivalent to intact S5 in their ability to stimulate NK activity, demonstrating that cross-linking of CD44 was not a necessary component of stimulation, and that nonspecific agglutination of target and effector cells was not occurring via the two F(ab) arms. The enhancement of NK function was monocyte-independent and mediated by radioresistant cells, indicating that the antibody enhanced NK cells directly. This finding would suggest that CD44 can direct a transmembrane signal for NK cell activation.
在本研究中，我们以犬外周血单核细胞（PBMC）作为效应细胞，检测了抗CD44单克隆抗体S5对自然杀伤（NK）功能的体外作用。S5以剂量依赖性和快速的方式增强了NK活性，识别CD44上共同表位的另一种抗CD44单克隆抗体IM7也有同样的作用。其他识别与S5和IM7不同表位的抗CD44单克隆抗体（Hermes-1和S3）对NK活性有不同的影响。只有在使用NK敏感靶细胞时，S5才会激活增强的杀伤作用，这表明未诱导出淋巴因子激活的杀伤细胞。抗体依赖性细胞毒性不是NK活性增强所涉及的机制，也不是Fc受体依赖性的，因为S5 F(ab')2能够增加NK活性。S5的F(ab')片段在刺激NK活性的能力上与完整的S5相当，这表明CD44的交联不是刺激的必要组成部分，并且靶细胞和效应细胞之间没有通过两个F(ab)臂发生非特异性凝集。NK功能的增强不依赖于单核细胞，且由抗辐射细胞介导，表明该抗体直接增强了NK细胞。这一发现表明CD44可以为NK细胞激活传导跨膜信号。
