Rakhmilevich A L
Trudeau Institute, Saranac Lake, New York 12983.
Transplantation. 1994 Jul 15;58(1):72-80.
The ability of anti-T cell mAb therapy to prevent acute rejection of a tumor allograft was studied. Injection of both anti-CD4 and anti-CD8 rat Ig2b mAbs 1 day before intraperitoneal implantation of P815 tumor cells into AB6F1 mice prevented tumor rejection in most of the mice. However, injection of the same mAbs on day 8 of tumor growth, i.e., 2 days before the onset of tumor rejection, failed to prevent rapid elimination of P815 cells from the peritoneal cavity. Flow cytometric analysis revealed that whereas splenic T cells remained depleted in these mice for up to 6 days after mAb injection, peritoneal T cells returned to control levels in 4-6 days. Moreover, a significant number of rat IgG+ cells were found in the peritoneal cavity 2 days after mAb administration, thus demonstrating that T cells were not depleted but coated with the mAbs at that time. The antitumor activity of the mAb-coated T cells was not impaired, in that CD8+ peritoneal cells from mice rejecting allogeneic P815 tumor on day 10, and rat IgG+ peritoneal cells taken from mice 2 days after giving them anti-CD8 mAb on day 8, were similarly highly cytotoxic against P815 cells in vitro. Taken together, the results demonstrate that the failure of anti-T cell mAb therapy to prevent the acute rejection of allogeneic P815 tumor was associated with resistance of T cells at the site of rejection to the action of anti-T cell mAbs in vivo.
研究了抗T细胞单克隆抗体疗法预防肿瘤同种异体移植急性排斥反应的能力。在将P815肿瘤细胞腹腔内植入AB6F1小鼠前1天注射抗CD4和抗CD8大鼠Ig2b单克隆抗体，可防止大多数小鼠发生肿瘤排斥反应。然而，在肿瘤生长第8天，即肿瘤排斥反应开始前2天注射相同的单克隆抗体，未能阻止P815细胞从腹腔中快速清除。流式细胞术分析显示，虽然在这些小鼠中，脾脏T细胞在注射单克隆抗体后长达6天仍保持耗竭状态，但腹腔T细胞在4 - 6天内恢复到对照水平。此外，在注射单克隆抗体后2天，在腹腔中发现大量大鼠IgG⁺细胞，从而表明此时T细胞并未被耗竭而是被单克隆抗体包被。包被有单克隆抗体的T细胞的抗肿瘤活性并未受损，因为在第10天排斥同种异体P815肿瘤的小鼠的CD8⁺腹腔细胞，以及在第8天给予抗CD8单克隆抗体后2天从小鼠获取的大鼠IgG⁺腹腔细胞，在体外对P815细胞同样具有高度细胞毒性。综上所述，结果表明抗T细胞单克隆抗体疗法未能预防同种异体P815肿瘤急性排斥反应与排斥部位的T细胞在体内对抗T细胞单克隆抗体作用的抗性有关。
