Leshem B, Lebendiker Z, Weiss L, Slavin S, Kedar E
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Bone Marrow Transplant. 1987 Aug;2(2):123-32.
Immunosuppression is believed to play a role in the maintenance of stable bone marrow (BM) chimeras. This study investigates the nature and specificity of the suppression that lymphocytes from allogeneic BM chimeras exert upon the alloreactivity of donor and recipient lymphocytes. Lethally irradiated CBA/J (H-2k) mice were infused with 10(7) unseparated (WBM) or T cell-depleted BM (TDBM) cells of B10.BR mice (H-2k, disparate at minor histocompatibility antigens). Mixtures consisting of spleen cells (SC) from BM chimeras and SC from either normal donor, recipient, or third party (C3H, H-2k) mice, were sensitized with irradiated BALB/c (H-2d) leukocytes, then assayed for proliferative and anti-H-2d cytotoxic activity and compared with those of appropriate control cultures. The alloreactivity of all three types of normal SC was non-specifically suppressed by SC from both WBM and TDBM chimeras taken 2 weeks post-BM transplantation (BMT). In contrast, at 4 weeks post-BMT, SC from both chimeras suppressed the alloreactivity of recipient-type cells whereas only SC from WBM, but not from TDBM chimeras, suppressed normal donor-type response, and neither could suppress the response of normal third party cells. The suppression of donor-type alloreactivity diminished with time, while that exerted on recipient-type lasted for at least 10 weeks post-BMT. The suppression of donor alloreactivity was mediated by radioresistant Thy1.2+, Lyt1+2+ cells while that exerted upon recipient's alloreactivity was mediated by radiosensitive Thy1.2+, Lyt1+2- cells. Both types of suppressor cells were of donor origin. The potential biological role of the suppressive activity in the engraftment of allogeneic BM is discussed.
免疫抑制被认为在维持稳定的骨髓（BM）嵌合体中发挥作用。本研究调查了同种异体BM嵌合体的淋巴细胞对供体和受体淋巴细胞的同种异体反应性所施加的抑制的性质和特异性。对经致死剂量照射的CBA/J（H-2k）小鼠输注10⁷个未分离的（全骨髓，WBM）或T细胞去除的B10.BR小鼠（H-2k，在次要组织相容性抗原上不相合）的骨髓（TDBM）细胞。将由BM嵌合体的脾细胞（SC）与来自正常供体、受体或第三方（C3H，H-2k）小鼠的SC组成的混合物，用经照射的BALB/c（H-2d）白细胞致敏，然后检测其增殖和抗H-2d细胞毒性活性，并与适当的对照培养物进行比较。在骨髓移植（BMT）后2周，来自WBM和TDBM嵌合体的SC非特异性地抑制了所有三种类型正常SC的同种异体反应性。相反，在BMT后4周，来自两种嵌合体的SC抑制了受体型细胞的同种异体反应性，而只有来自WBM嵌合体而非TDBM嵌合体的SC抑制了正常供体型反应，且两者均不能抑制正常第三方细胞的反应。对供体型同种异体反应性的抑制随时间减弱，而对受体型的抑制在BMT后至少持续10周。对供体同种异体反应性的抑制由辐射抗性的Thy1.2⁺、Lyt1⁺2⁺细胞介导，而对受体同种异体反应性的抑制由辐射敏感的Thy1.2⁺、Lyt1⁺2⁻细胞介导。两种类型的抑制细胞均来源于供体。讨论了抑制活性在同种异体BM植入中的潜在生物学作用。
