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 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.
D000818:Animals; D003114:Colony-Forming Units Assay; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006082:Graft Enhancement, Immunologic; D018380:Hematopoietic Stem Cell Transplantation; D016219:Immunotherapy, Adoptive; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016853:Muromonab-CD3 / Q000494:pharmacology*; D011828:Radiation Chimera; D011833:Radiation Injuries, Experimental / Q000276:immunology / Q000628:therapy*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000637:transplantation*; D014916:Whole-Body Irradiation / Q000009:adverse effects
D016853:Muromonab-CD3