Nr. Jin et al., ANTI-CD3-ACTIVATED SPLENOCYTES ENHANCE SURVIVAL IN LETHALLY IRRADIATED MICE AFTER TRANSPLANT OF SYNGENEIC HEMATOPOIETIC STEM-CELLS, Experimental hematology, 23(13), 1995, pp. 1331-1336
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.