Jin N R, Lum L G, Ratanatharathorn V, Sensenbrenner L L
Immunotherapy Program, St. Luke's Medical Center, Milwaukee, WI 53201-2901, USA.
Exp Hematol. 1995 Dec;23(13):1331-6.
Although cytokines produced by activated T cells may accelerate immunohematopoietic reconstitution after autologous bone marrow transplantation (ABMT), there is no direct evidence that infusion of anti-CD3 mAb-activated T cells can accelerate engraftment by hematopoietic stem cells. This study tests the ability of anti-CD3-activated murine splenocytes (ASC) to enhance the rescue of lethally irradiated (9 Gy) BDF1 mice by transplant of a limiting dose of fresh unmanipulated syngeneic splenocytes (SC). A minority (14.8%, 10-25%) of mice could be rescued with 5 x 10(5) SC after 9 Gy total-body irradiation (TBI). When 10(6) or 10(7) ASC were added to 5 x 10(5) SC, survival increased to 50% in those that received 5 x 10(5) SC + 10(6) ASC (not significant [NS]) and to 81.4% (77.7-88.0%) in those that received 5 x 10(5) SC + 10(7) ASC (p < 0.001). Furthermore, adding a fixed dose of 10(7) ASC to increasing doses of SC (10(5), 5 x 10(5), and 10(6)) enhanced survival at the different doses of SC. ASC alone did not rescue mice. CD3+ cells were the predominant population (77.6 +/- 6.7%) in the ASC inoculum, while NK cells remained low (1.2 +/- 0.9%). Colony-forming unit-spleen (CFU-S) yield after injection of SC showed dose dependence, whereas injection of 10 x 10(6) ASC alone failed to show any CFU-S yield in 23 of 25 recipient spleens. These results show that ASC enhanced survival of mice rescued with limiting doses of SC and that this effect was ASC dose-dependent but not dependent on the addition of extra stem cells.
尽管活化T细胞产生的细胞因子可能会加速自体骨髓移植（ABMT）后的免疫造血重建，但尚无直接证据表明输注抗CD3单克隆抗体激活的T细胞能够加速造血干细胞的植入。本研究测试了抗CD3激活的小鼠脾细胞（ASC）通过移植有限剂量的新鲜未处理同基因脾细胞（SC）来增强对致死性照射（9 Gy）的BDF1小鼠的挽救能力。在9 Gy全身照射（TBI）后，少数（14.8%，10 - 25%）小鼠可通过5×10⁵个SC获救。当将10⁶或10⁷个ASC添加到5×10⁵个SC中时，接受5×10⁵个SC + 10⁶个ASC的小鼠存活率增至50%（无显著性差异[NS]），而接受5×10⁵个SC + 10⁷个ASC的小鼠存活率增至81.4%（77.7 - 88.0%）（p < 0.001）。此外，将固定剂量的10⁷个ASC添加到递增剂量的SC（10⁵、5×10⁵和10⁶）中，可提高不同剂量SC时的存活率。单独的ASC不能挽救小鼠。ASC接种物中CD3⁺细胞是主要群体（77.6±6.7%），而NK细胞数量仍然很低（1.2±0.9%）。注射SC后的脾集落形成单位（CFU - S）产量呈剂量依赖性，而单独注射10×10⁶个ASC时，25个受体脾脏中有23个未显示出任何CFU - S产量。这些结果表明，ASC提高了用有限剂量SC挽救的小鼠的存活率，且这种作用是ASC剂量依赖性的，但不依赖于额外干细胞的添加。
