紫外线B照射供体特异性输血及大鼠心脏移植后由CD8 + 抑制性T细胞介导的感染性耐受

Infectious tolerance mediated by CD8+ T-suppresor cells after UV-B-irradiated donor-specific transfusion and rat heart transplantation.

作者信息

Witkowski P, Liu J W, Jin M X, Liu Z, Suciu-Foca N, Hardy M A

机构信息

Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.

出版信息

Transplant Proc. 2005 Jan-Feb;37(1):43-5. doi: 10.1016/j.transproceed.2004.12.081.

DOI:10.1016/j.transproceed.2004.12.081

PMID:15808541

Abstract

AIMS

CD8+CD28- human T-suppressor cells (Ts), which can be generated in vitro, act directly on APC rendering them tolerogenic to unprimed and primed CD4+ T cells. The aim of this study was to investigate the possibility that CD8+ T cells mediate the induction of tolerance in a heart transplantation model in rodents.

MATERIALS AND METHODS

Blood from Lewis rats was UV-B-irradiated and transfused into ACI recipients on days -21, -14, and -7 before heart allograft transplantation on day 0. CD4(+) and CD8(+) T cells were positively selected from ACI rats, which had tolerated Lewis heart allografts for more than 100 days and were adoptively transferred to naive ACI rats pretreated (day -1) with gamma irradiation. These ACI rats underwent transplantation with Lewis hearts 24 hours after adoptive transfer of putative T-suppressor cells.

RESULTS

Adoptive transfer of CD8(+) T cells from tolerant ACI to naive ACI rats significantly prolonged Lewis heart mean allograft survival time (MST +/- SD) to 69 +/- 13 days as compared with 15 +/- 1 and 14 +/- 1 days in animals adoptively transferred with CD4+ T cells or untreated controls, respectively (P < .001). Similarly, adoptive transfer of CD8(+) T cells from secondary ACI recipients to naive syngeneic animals also significantly prolonged survival of heart allografts to MST +/- SD of 72 +/- 4 for CD8(+) and 15 +/- 4 days for CD4(+) T cells (P < .001).

CONCLUSIONS

These data demonstrate that allogeneic tolerance induced in ACI recipients by treatment with UV-B-irradiated blood from Lewis donors is mediated by CD8+ T-suppressor cells.

摘要

目的

体外产生的CD8⁺CD28⁻人T抑制细胞（Ts）可直接作用于抗原呈递细胞（APC），使其对未致敏和已致敏的CD4⁺T细胞产生耐受性。本研究的目的是探讨CD8⁺T细胞在啮齿动物心脏移植模型中介导耐受性诱导的可能性。

材料与方法

在心脏同种异体移植手术日（第0天）前的第-21、-14和-7天，将经紫外线B照射的Lewis大鼠血液输注到ACI受体中。从耐受Lewis心脏同种异体移植超过100天的ACI大鼠中阳性选择CD4⁺和CD8⁺T细胞，并将其过继转移到经γ射线照射预处理（第-1天）的未致敏ACI大鼠中。这些ACI大鼠在过继转移假定的T抑制细胞24小时后接受Lewis心脏移植。

结果

将来自耐受ACI大鼠的CD8⁺T细胞过继转移到未致敏ACI大鼠中，与分别过继转移CD4⁺T细胞的动物或未处理对照相比，显著延长了Lewis心脏平均同种异体移植存活时间（MST±SD）至69±13天，而CD4⁺T细胞过继转移组和未处理对照组的存活时间分别为15±1天和14±1天（P<0.001）。同样，将来自二次ACI受体的CD8⁺T细胞过继转移到未致敏的同基因动物中，也显著延长了心脏同种异体移植的存活时间，CD8⁺T细胞组的MST±SD为72±4天，CD4⁺T细胞组为15±4天（P<0.001）。