Interleukin-1 enhances survival of lethally irradiated mice treated with allogeneic bone marrow cells
Interleukin-1 enhances survival of lethally irradiated mice treated with allogeneic bone marrow cells
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Interleukin-1 可提高用同种异体骨髓细胞治疗的致命辐射小鼠的存活率
DOI：
10.1182/blood.v74.6.2257.2257
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发表时间：
1989
期刊：
影响因子：
20.3
通讯作者：
D. Longo
中科院分区：
文献类型：
--
作者：
J. Oppenheim;R. Neta;P. Tiberghien;R. Gress;J. Kenny;D. Longo
白细胞介素-1（IL-1）增强了同种异体骨髓（BM）细胞的能力，以促进给予辐射剂量（1，200至1，350 cGy）的小鼠的存活率，该剂量显著高于通常用于BM消融的剂量（850至950 cGy）。如果在辐射前20小时或辐射后1至3小时也用10微克IL-1的单次腹膜内（IP）剂量治疗，给予10（7）个T细胞耗尽的Balb/c（H-2d）BM细胞的致死辐射（1，200至1，350 cGy）C57 B1/6（H-2b）小鼠存活6周以上，则存活率为3至5倍。这些小鼠的脾脏主要但不完全用供体细胞重建（54%至91%）。对存活超过6周的小鼠的表皮和胃肠道组织进行组织学检查，未发现任何移植物抗宿主（GVH）疾病的证据;然而，由于10%至43%的小鼠在第30至46天死亡，因此不能排除这些小鼠中GVH综合征的可能性。给予骨髓移植和IL-1的照射小鼠的脾细胞（由大于或等于85%的供体细胞组成）能够产生特异性T细胞细胞毒性杀伤无关的同种异体供体细胞，但对携带宿主或供体主要组织相容性复合体（MHC）I类抗原的靶细胞不反应。因此，长期混合嵌合体存活者耐受受体和供体同种异体抗原，但表现出免疫能力。这些结果表明，IL-1促进致死照射小鼠的存活，并且这些动物中的同种异体造血细胞对宿主MHC抗原产生耐受性。虽然有许多未回答的问题，这些数据表明，IL-1可能被证明在促进骨髓移植的临床有用。
Interleukin-1 (IL-1) enhanced the capacity of allogeneic bone marrow (BM) cells to promote survival of mice given doses of radiation (1,200 to 1,350 cGy) that are significantly higher than those generally used for BM ablation (850 to 950 cGy). Three to five times greater numbers of lethally irradiated (1,200 to 1,350 cGy) C57B1/6 (H-2b) mice given 10(7) T-cell-depleted Balb/c (H-2d) BM cells survived over 6 weeks if also treated with a single intraperitoneal (IP) dose of 10 micrograms IL-1 20 hours before or from 1 to 3 hours after radiation. The spleens of these mice were reconstituted predominantly, but not exclusively, with donor cells (54% to 91%). Histologic examination of the epidermal and gastrointestinal tissues of mice surviving more than 6 weeks did not reveal any evidence of graft-versus-host (GVH) disease; however, since 10% to 43% of the mice died between days 30 and 46, the possibility of a GVH syndrome in these mice cannot be excluded. The spleen cells from irradiated mice given BM transplants and IL-1, which consisted of greater than or equal to 85% donor cells, were able to generate specific T-cell cytotoxic killing of unrelated allogeneic donor cells but were unreactive to target cells bearing either host or donor major histocompatibility complex (MHC) class I antigens. Thus, long-term mixed chimeric survivors were tolerant to recipient and donor alloantigens but exhibited immunologic competence. These results show that IL-1 promotes survival of lethally irradiated mice and that allogeneic hematopoietic cells in such animals develop tolerance to host MHC antigens. Although there are many unanswered questions, these data suggest that IL-1 may prove clinically useful in promoting BM engraftment.