Inhibition of antiskin allograft immunity by infusions with syngeneic photoinactivated effector lymphocytes.

Inhibition of antiskin allograft immunity by infusions with syngeneic photoinactivated effector lymphocytes.
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通过输注同基因光灭活效应淋巴细胞抑制抗皮肤同种异体移植免疫。

DOI:
10.1111/1523-1747.ep12696853
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发表时间:
1989
期刊:
The Journal of investigative dermatology
影响因子:
--
通讯作者:
Berger,C
Berger,C
中科院分区:
--
文献类型:
--
作者:
Perez,M;Edelson,R;Laroche,L;Berger,C

文献摘要

被引文献

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诱导同种异体皮肤移植耐受需要选择性抑制宿主对外源组织相容性抗原的反应。本报告描述了一种新的方法,采用预处理的效应细胞与8-甲氧基-补骨脂素(8-MOP)和紫外线A光(UVA),使效应细胞的移植排斥免疫原性的同基因受体。光损伤细胞的再输注导致免疫抑制宿主反应,允许组织不相容性皮肤移植物的长期保留,并特异性抑制与同种异体移植物排斥相关的体外和体内反应。BALB/c小鼠接受CBA/j皮肤移植物后8天,其脾细胞作为同种异体反应性效应细胞的来源。脾细胞用100 ng/ml 8-MOP和1 J/cm 2 UVA处理,然后再输注到幼稚BALB/c受体中。在混合白细胞培养(MLC)、细胞毒性(CTL)、迟发型超敏反应试验(DTH)、来自含有CBA/j同种异体抗原排斥效应细胞的光灭活脾细胞的BALB/c受体的脾细胞在MLC中增殖不良,并且产生对CBA/j同种异体抗原排斥效应细胞的较低的细胞毒性T细胞应答。j同种异体抗原与致敏和幼稚对照相比。这些低应答小鼠的脾细胞抑制了致敏和幼稚BALB/c小鼠对同种异体抗原的MLC和CTL应答。与对照组相比,在体内特异性抑制DTH反应的相关同种异体抗原。此外,以这种方式治疗的BALB/c小鼠在移植后保留CBA/j皮肤移植物长达42天,没有明显的排斥反应。这些结果表明,在体内和体外的同种异体抗原的反应,可以通过预处理与光灭活的脾细胞含有同种异体抗原排斥反应的效应细胞的主机减弱。
Induction of tolerance for skin allotransplantation requires selective suppression of the host response to foreign histo-compatibility antigens. This report describes a new approach that employs pretreatment of effector cells with 8-methoxy-psoralen (8-MOP) and ultraviolet A light (UVA) to render the effector cells of graft rejection immunogenic for the syngeneic recipient. Reinfusion of photodamaged cells resulted in an immunosuppressive host response that permitted prolonged retention of histoincompatible skin grafts and specifically inhibited in vitro and in vivo responses that correlate with allograft rejection.Eight days after BALB/c mice received CBA/j skin grafts, their splenocytes served as a source of alloreactive effector cells. The splenocytes were treated with 100 ng/ml8-MOP and 1 J/cm2UVA before reinfusion into naive BALB/c recipients. Recipient mice were tested for tolerance to alloantigens in mixed leukocyte culture (MLC), cytotoxicity (CTL), delayed type hypersensitivity assays (DTH), and challenge with a fresh CBA/j graft.Splenocytes from BALB/c recipients of photoinactivated splenocytes containing the effector cells of CBA/j alloantigen rejection proliferated poorly in MLC and generated lower cytotoxic T cell responses to CBA/j alloantigens in comparison with sensitized and naive controls. Splenocytes from these hyporesponsive mice suppressed the MLC and CTL response to alloantigen from sensitized and naive BALB/c mice. In vivo the DTH response was specifically suppressed to the relevant alloantigen in comparison with controls. Moreover, BALB/c mice treated in this fashion retained a CBA/j skin graft for up to 42 d posttransplantation without visual evidence of rejection. These results indicate that the in vivo and in vitro response to alloantigen can be attenuated by pretreating the host with photoinactivated splenocytes containing the effector cells of alloantigen rejection.