Rigney M E, Gignac M R, Gritsch H A, Chatlos L J, Hoffman R A, Jordan M L
Meegan Lynch Hickey Lab for Life, Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania, USA.
Transplantation. 1996 Dec 15;62(11):1601-5. doi: 10.1097/00007890-199612150-00013.
Much interest has recently focused on administration of donor cells with organ transplantation to improve graft outcome. However, whether donor cell administration actually confers donor-specific (DS) hyporeactivity is unknown. The intra-graft events after DS bone marrow (BM) infusion were therefore examined in an in vivo sponge matrix allograft model. Recipient C57BL/6J (B6,H2b) mice (five per group) received either media alone, 10(7) syngeneic (B6), or allogeneic (DBA/2J,H2d) BM cells intravenously. Seven days later, a sponge matrix allograft containing 10(7) allogeneic (DBA) splenocytes was implanted. On various days after grafting, graft-infiltrating cells were tested for in vitro cytotoxicity by 51Cr release assay. Previous DSBM infusion significantly reduced intragraft allospecific cytolytic T-cell (CTL) activity compared with mice receiving syngeneic BM or media alone (3.5 +/- 5.1% vs. 46.2 +/- 13.3% and 47.9 +/- 13.5% at 100:1 E:T, respectively, P < 0.001). Time course studies showed that DSBM impaired allospecific CTL activity whether given on day -10 (3.3% at 100:1 E:T), day -7 (2.2%), day -2(7.7%), or day 0 (6.5%), but was not as effective when given on day +7 (27.1%). Flow cytometry of graft-infiltrating cells on day +12 showed a decreased percentage of CD8+ cells after DSBM, compared with syngeneic BM or media alone (13.1% vs. 38.0% and 36% respectively, P = 0.01), but the percentage of CD4+ cells was similar in all groups (5.5%, 6.9%, and 4%, respectively). Thus, (1) DSBM inhibits allospecific CTL development in the allograft, (2) decreased intra-graft CTL activity after DSBM correlates with a decreased percentage of intragraft CD8+ cells, and (3) DSBM induces hyporeactivity up until the day of the allograft placement, but not thereafter. DSBM may, thus, induce graft hyporeactivity by impairing intragraft immune activation.
最近，很多研究兴趣都集中在通过器官移植时输入供体细胞来改善移植物的转归。然而，输入供体细胞是否真的能诱导供体特异性（DS）低反应性尚不清楚。因此，我们在一个体内海绵基质同种异体移植模型中研究了DS骨髓（BM）输注后的移植物内事件。受体C57BL/6J（B6，H2b）小鼠（每组5只）静脉内分别输注单纯培养基、10⁷个同基因（B6）或异基因（DBA/2J，H2d）BM细胞。7天后，植入含有10⁷个异基因（DBA）脾细胞的海绵基质同种异体移植物。在移植后的不同时间，通过⁵¹Cr释放试验检测移植物浸润细胞的体外细胞毒性。与接受同基因BM或单纯培养基的小鼠相比，先前的DSBM输注显著降低了移植物内同种异体特异性细胞毒性T细胞（CTL）活性（在效靶比为100:1时分别为3.5±5.1% vs. 46.2±13.3%和47.9±13.5%，P<0.001）。时间进程研究表明，无论在第-10天（效靶比为100:1时为3.3%）、第-7天（2.2%）、第-2天（7.7%）还是第0天（6.5%）给予DSBM，均会损害同种异体特异性CTL活性，但在第+7天给予时效果不佳（27.1%）。移植后第12天对移植物浸润细胞进行流式细胞术检测显示，与同基因BM或单纯培养基相比，DSBM处理后CD8⁺细胞百分比降低（分别为13.1% vs. 38.0%和36%，P = 0.01），但所有组中CD4⁺细胞百分比相似（分别为5.5%、6.9%和4%）。因此，（1）DSBM抑制同种异体移植物中同种异体特异性CTL的发育，（2）DSBM处理后移植物内CTL活性降低与移植物内CD8⁺细胞百分比降低相关，（3）DSBM在同种异体移植放置日之前均可诱导低反应性，但之后则不然。因此，DSBM可能通过损害移植物内免疫激活来诱导移植物低反应性。
