Aksentijevich I, Sachs D H, Sykes M
Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1991 Dec 15;147(12):4140-6.
Specific tolerance can be induced in animals by transplanting hemopoietic cells across concordant species barriers. Despite the fact that the rat-mouse species combination is considered concordant, we have recently demonstrated that normal murine serum contains natural antibodies (nAb), predominantly of the IgM and IgG3 subclasses, with markedly greater binding to rat bone marrow cells (BMC) than to rat splenocytes or thymocytes. Since much greater numbers of rat BMC than of allogeneic murine BMC are required to achieve engraftment in mice, we considered the possibility that these nAbs might be responsible, and that the increased numbers of BMC might be required to absorb these nAb. To evaluate the effect of these nAb on engraftment of rat BMC in mice, we have now performed adoptive transfer studies using T and B cell-deficient severe combined immunodeficiency disease (SCID) mice as recipients. Administration of as few as 5 x 10(5) T cell-depleted rat BMC led to induction of stable xenochimerism in SCID mice conditioned with 4-Gy whole body irradiation. Rat T cells developed after a delay of several weeks, and conferred the ability to reject non-donor-type rat skin grafts, whereas donor-type grafts were accepted. Adoptive transfer of 4 ml of normal BALB/c serum led to a marked reduction in the level of rat chimerism in SCID recipients of 2 x 10(6) F344 BMC. The ability of sera to inhibit engraftment of rat BMC correlated with their cytotoxic nAb content, and the inhibitory effect of highly cytotoxic sera could be overcome by administration of large numbers of rat BMC. Thus, normal mouse serum has a limited ability to hinder engraftment of rat BMC, and this degree of resistance can be overcome by adsorption when large numbers of BMC are administered. Eliminating nAb from serum may be more difficult in discordant species combinations in recipients with functional B cells, but may likewise permit the use of BMT as a means of inducing transplantation tolerance.
通过跨越适宜物种屏障移植造血细胞，可在动物体内诱导出特异性耐受。尽管大鼠 - 小鼠物种组合被认为是适宜的，但我们最近发现，正常小鼠血清中含有天然抗体（nAb），主要为IgM和IgG3亚类，与大鼠骨髓细胞（BMC）的结合明显强于与大鼠脾细胞或胸腺细胞的结合。由于在小鼠体内实现植入所需的大鼠BMC数量比同种异体小鼠BMC多得多，我们推测这些nAb可能起了作用，且可能需要增加BMC数量来中和这些nAb。为评估这些nAb对大鼠BMC在小鼠体内植入的影响，我们现在使用T细胞和B细胞缺陷的严重联合免疫缺陷病（SCID）小鼠作为受体进行了过继转移研究。给予低至5×10⁵个去除T细胞的大鼠BMC，就能在接受4 - Gy全身照射预处理的SCID小鼠中诱导出稳定的异种嵌合体。大鼠T细胞在数周后出现，并赋予了排斥非供体类型大鼠皮肤移植的能力，而供体类型的移植则被接受。过继转移4 ml正常BALB / c血清会导致接受2×10⁶个F344 BMC的SCID受体中大鼠嵌合体水平显著降低。血清抑制大鼠BMC植入的能力与其细胞毒性nAb含量相关，大量给予大鼠BMC可克服高细胞毒性血清的抑制作用。因此，正常小鼠血清阻碍大鼠BMC植入的能力有限，当给予大量BMC时，这种抵抗程度可通过吸附来克服。在具有功能性B细胞的受体中，消除血清中的nAb在不相容物种组合中可能更困难，但同样可能允许使用骨髓移植作为诱导移植耐受的一种手段。
