Anti-CD3-activated splenocytes enhance survival in lethally irradiated mice after transplant of syngeneic hematopoietic stem cells
| Autor: | N R, Jin, L G, Lum, V, Ratanatharathorn, L L, Sensenbrenner |
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| Rok vydání: | 1995 |
| Předmět: |
Dose-Response Relationship
Immunologic Hematopoietic Stem Cell Transplantation Lymphocyte Activation Immunotherapy Adoptive Colony-Forming Units Assay Mice Inbred C57BL Mice Radiation Injuries Experimental Graft Enhancement Immunologic Mice Inbred DBA T-Lymphocyte Subsets Radiation Chimera Animals Female Spleen Whole-Body Irradiation Muromonab-CD3 |
| Zdroj: | Experimental hematology. 23(13) |
| ISSN: | 0301-472X |
| Popis: | 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 (p0.001). 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. |
| Databáze: | OpenAIRE |
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