ANTI-CD3-ACTIVATED SPLENOCYTES ENHANCE SURVIVAL IN LETHALLY IRRADIATED MICE AFTER TRANSPLANT OF SYNGENEIC HEMATOPOIETIC STEM-CELLS

Although cytokines produced by activated T cells may accelerate immuno hematopoietic reconstitution after autologous bone marrow transplantat ion (ABMT), there is no direct evidence that infusion of anti-CD3 mAb- activated T cells can accelerate engraftment by hematopoietic stem cel ls. This study tests the ability of anti-CD3-activated murine splenocy tes (ASC) to enhance the rescue of lethally irradiated (9 Gy) BDF1 mic e by transplant of a limiting dose of fresh unmanipulated syngeneic sp lenocytes (SC). A minority (14.8%, 10-25%) of mice could be rescued wi th 5x10(5) SC after 9 Gy total-body irradiation (TBI). When 10(6) or 1 0(7) ASC were added to 5x10(5) SC, survival increased to 50% in those that received 5x10(5) SC + 10(6) ASC (not significant [NS]) and to 81. 4% (77.7-88.0%) in those that received 5x10(5) SC + 10(7) ASC (p < 0.0 01). Furthermore, adding a fixed dose of 10(7) ASC to increasing doses of SC (10(5), 5x10(5), and 10(6)) enhanced survival at the different doses of SC. ASC alone did not rescue mice. CD3(+) cells were the pred ominant 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 x10(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.