Dennert G, Anderson C G, Warner J
J Immunol. 1986 Jun 1;136(11):3981-6.
Acute marrow graft rejection in allogeneic or semiallogeneic donor-recipient mouse combinations has been suggested to be caused by natural killer (NK) cells. The unique in vitro specificity of NK cells for tumor cells, however, does not explain the specific rejection of bone marrow grafts by NK cells. Recent experiments have implicated antibody in marrow graft recipients as the specificity-inducing component that guides NK cells in an antibody-dependent cytotoxic (ADCC) reaction to attack the marrow graft. On the basis of this hypothesis, one would postulate that nonresponder marrow graft recipients can be converted into responders by injection with antibody of appropriate specificity. Results presented in this report show that this is indeed possible. Specific monoclonal or polyclonal antibody of IgG isotype induces marrow graft rejection in nonresponder recipients. This can be demonstrated in allogeneic as well as in semi-allogeneic (hybrid resistance) donor-recipient strain combinations. Antibody-induced marrow graft rejection is independent of complement and dependent on the presence of NK cells. Surprisingly, graft rejection induced by antibody is quite efficient in allogeneic and semiallogeneic marrow donor-recipient combinations, whereas it is generally poor in syngeneic combinations. This result is not understood if NK cells lyse bone marrow cells solely in an ADCC-type reaction. Because NK cells can lyse targets in an antibody-dependent as well as independent reaction, it is proposed that the binding of NK cells to targets via their receptors plays an additional role in the rejection of bone marrow in vivo. Preliminary evidence for this possibility is that NK cells in the apparent absence of antibody may have a detectable suppressive effect on the growth of marrow grafts in F1 hybrid mice transplanted with parental marrow grafts.
在同种异体或半同种异体供体 - 受体小鼠组合中，急性骨髓移植排斥反应被认为是由自然杀伤（NK）细胞引起的。然而，NK细胞对肿瘤细胞独特的体外特异性并不能解释NK细胞对骨髓移植的特异性排斥。最近的实验表明，骨髓移植受体中的抗体是诱导特异性的成分，它在抗体依赖性细胞毒性（ADCC）反应中引导NK细胞攻击骨髓移植。基于这一假设，可以推测无反应性骨髓移植受体可以通过注射具有适当特异性的抗体而转变为有反应性的受体。本报告中呈现的结果表明这确实是可能的。IgG同种型的特异性单克隆或多克隆抗体可在无反应性受体中诱导骨髓移植排斥。这在同种异体以及半同种异体（杂种抗性）供体-受体品系组合中都可以得到证明。抗体诱导的骨髓移植排斥与补体无关，且依赖于NK细胞 的存在。令人惊讶的是，抗体诱导的移植排斥在同种异体和半同种异体骨髓供体 - 受体组合中相当有效，而在同基因组合中通常较差。如果NK细胞仅在ADCC型反应中裂解骨髓细胞，那么这个结果就无法解释。因为NK细胞可以在抗体依赖性以及非依赖性反应中裂解靶标，所以有人提出NK细胞通过其受体与靶标的结合在体内骨髓排斥中起额外作用。支持这种可能性的初步证据是，在明显没有抗体的情况下，NK细胞可能对移植了亲代骨髓移植物的F1杂种小鼠中骨髓移植物的生长具有可检测到的抑制作用。
