胸腺切除对胸腺内注射供体脾细胞诱导的耐受性的预防作用。

Nakafusa Y, Goss J A, Flye M W

Department of Surgery, Washington University School of Medicine, St Louis, MO.

Surgery. 1993 Aug;114(2):183-9; discussion 189-90.

BACKGROUND

We have recently demonstrated indefinite donor-specific cardiac allograft survival after the intrathymic injection of donor splenocytes and simultaneous injection of antilymphocyte serum (ALS) in a fully major histocompatibility complex-mismatched rat combination. In this study we performed thymectomy to determine the length of time required for donor alloantigen to be present in the recipient thymus to induce tolerance.

METHODS

Male Buffalo (BUF; RT1b) rats at 4 to 8 weeks of age underwent intrathymic injection of 25 x 10(6) Lewis (LEW; RT1(1)) splenocytes and simultaneously received an intraperitoneal injection of 1 ml ALS. To determine the kinetics of tolerance induction, the BUF recipients underwent thymectomy on days 1, 3, or 7 after the initial intrathymic injection of alloantigen and intraperitoneal ALS. Twenty-one days after intrathymic alloantigen injection and ALS, all rats underwent transplantation with a heterotopic LEW cardiac allograft.

RESULTS

Thymectomy performed 1 (mean survival time, 6.8 days) and 3 (mean survival time, 8.0 days) days after donor alloantigen injection and ALS did not affect the normal rejection of LEW cardiac allografts. In contrast, thymectomy 7 days after intrathymic alloantigen injection and ALS resulted in indefinite survival of cardiac allografts in 75% of recipients (mean survival time > 77.0 days). In addition, allospecific cytotoxic T lymphocyte activity and interleukin-2 production were markedly decreased in those recipients undergoing thymectomy after 7 days compared with untreated control rats and recipients undergoing thymectomy 1 and 3 days after alloantigen injection.

CONCLUSIONS

The presence of the thymus for at least 7 days after intrathymic alloantigen injection and intraperitoneal ALS allows the development of indefinite donor-specific cardiac allograft tolerance.

背景

我们最近证明，在完全主要组织相容性复合体不匹配的大鼠组合中，胸腺内注射供体脾细胞并同时注射抗淋巴细胞血清（ALS）后，供体特异性心脏同种异体移植物可实现无限期存活。在本研究中，我们进行了胸腺切除术，以确定供体同种异体抗原在受体胸腺中存在多长时间才能诱导耐受。

方法

4至8周龄的雄性布法罗（BUF；RT1b）大鼠接受胸腺内注射25×10⁶ 只刘易斯（LEW；RT1¹）脾细胞，并同时接受腹腔注射1 ml ALS。为了确定耐受诱导的动力学，BUF受体在初次胸腺内注射同种异体抗原和腹腔注射ALS后的第1、3或7天接受胸腺切除术。胸腺内注射同种异体抗原和ALS 21天后，所有大鼠均接受异位LEW心脏同种异体移植。

结果

在供体同种异体抗原注射和ALS后第1天（平均存活时间为6.8天）和第3天（平均存活时间为8.0天）进行胸腺切除术，并不影响LEW心脏同种异体移植物的正常排斥反应。相比之下，胸腺内注射同种异体抗原和ALS后7天进行胸腺切除术，导致75%的受体心脏同种异体移植物无限期存活（平均存活时间>77.0天）。此外，与未治疗的对照大鼠以及在同种异体抗原注射后第1天和第3天进行胸腺切除术的受体相比，在7天后进行胸腺切除术的那些受体中，同种异体特异性细胞毒性T淋巴细胞活性和白细胞介素-2产生明显降低。