Kobayashi E, Kamada N, Enosawa S, Toyama N, Delriviere L, Goto S, Kim Y I, Miyata M
Department of Surgery, Jichi Medical School, Omiya Medical Centre, Japan.
Clin Exp Immunol. 1993 Jun;92(3):527-31. doi: 10.1111/j.1365-2249.1993.tb03432.x.
Although small bowel transplantation (SBT), or pancreas-spleen transplantation (PST) often lead to lethal graft-versus-host reaction (GVHR) in experimental animals, fatal GVHR is rare after clinical liver transplantation. This study describes a modified model of SBT and PST in the rat using cuff techniques applied to the renal artery and vein of the recipient. The ability of LEW (RT1(1)) or BN (RT1n) lymphocytes accompanying intestinal, splenic, or hepatic grafts to induce lethal GVHR in (LEW x BN) F1 hybrid recipients was compared. SBT and PST experiments showed that lethal GVHR always occurred in LEW-into-F1 combination, but was much less frequent in BN-into-F1 SBT. In mixed lymphocyte reaction (MLR), LEW mesenteric or splenic T cells showed significantly higher proliferative responses against BN stimulators than did BN mesenteric or splenic T cells against LEW. Adoptive cell transfer experiments using mesenteric or splenic cells also showed that LEW cells were higher responders than BN. In contrast with SBT and PST results, a lethal GVHR was not induced after liver or pancreas grafting alone in either parent-to-F1 combination. In MLR, hepatic T cells from either parent failed to elicit a proliferative response against allostimulators. These results indicate that the occurrence of lethal GVHR is dependent upon the reactivity of parental lymphocytes against allo-antigenicity of F1 hybrids and also upon the lymphoid tissue transplanted. The lack of alloreactivity of hepatic T cells accounts for the absence of lethal GVHR after liver grafting.
尽管小肠移植（SBT）或胰脾移植（PST）在实验动物中常导致致死性移植物抗宿主反应（GVHR），但临床肝移植后致命性GVHR却很少见。本研究描述了一种在大鼠中使用袖套技术应用于受体肾动脉和静脉的SBT和PST改良模型。比较了伴随肠、脾或肝移植的LEW（RT1(1)）或BN（RT1n）淋巴细胞在（LEW×BN）F1杂交受体中诱导致死性GVHR的能力。SBT和PST实验表明，致死性GVHR总是发生在LEW到F1的组合中，但在BN到F1的SBT中发生频率要低得多。在混合淋巴细胞反应（MLR）中，LEW肠系膜或脾T细胞对BN刺激物的增殖反应明显高于BN肠系膜或脾T细胞对LEW的反应。使用肠系膜或脾细胞的过继性细胞转移实验也表明，LEW细胞比BN细胞反应性更高。与SBT和PST结果相反，在任一亲代到F1的组合中，单独进行肝或胰腺移植后均未诱导出致死性GVHR。在MLR中，来自任一亲代的肝T细胞均未引发对同种异体刺激物的增殖反应。这些结果表明，致死性GVHR的发生取决于亲代淋巴细胞对F1杂种同种异体抗原性的反应性，也取决于移植的淋巴组织。肝T细胞缺乏同种异体反应性解释了肝移植后缺乏致死性GVHR的原因。
