Zakarian S, Billingham R E
J Exp Med. 1972 Dec 1;136(6):1545-63. doi: 10.1084/jem.136.6.1545.
Using guinea pigs of strains 2 and 13 and their F(1) hybrids as experimental subjects, various lines of evidence have been obtained that in this species, as in all others tested, the only significant cellular antigens with which donor lymphocytes engage when normal and immune lymphocyte reactions are incited are radiosensitive leukocytes. Constitutive cells of the skin are unimportant. (a) The intensities of these reactions in irradiated subjects are dependent upon the peripheral leukocyte concentration. When this falls below a certain threshold no reactions are incitable. (b) Highly leukopenic animals are capable of developing immune lymphocyte transfer (ILT) reactions if normal lymphoid cells of their own genetic constitution are mixed with the putative attacking donor cells, as "supplementing antigen," before inoculation. (c) Radiation-chimeric strain 13 animals having F(1) hybrid leukocytes in their bloodstream give typical ILT reactions when challenged intradermally with strain 13 anti-2 node cells. Exposure of strain 2 animals to 600 R does not prevent their becoming actively immunized if, 24 hr later, they are injected intradermally with strain 13 lymphocytes. However, this sensitization, revealed by the host's capacity to give delayed hypersensitivity reactions, wanes as leukopenia progresses. On the basis of this and other findings it is argued that the flare-up stage of the NLT reaction in preirradiated hosts is mainly an expression of host sensitivity against the transferred alien cells. Two unexpected observations have been made in the course of this study: (a) F(1) hybrid animals developed what appeared to be a strong delayed hypersensitivity after intradermal inoculation with parental strain lymphoid cells or antigenic extracts prepared from them. (b) If strain 13 guinea pigs which had been sensitized against strain 2 tissue antigens by intradermal injection of lymphocytes 7 days beforehand were inoculated intravenously with strain 2 antigenic extract a significant proportion of the animals developed severe delayed necrotizing reactions, recall flares, at some or all of the healed skin inoculation sites.
以2号和13号品系的豚鼠及其F(1)杂种作为实验对象,已获得了各种证据表明,在这个物种中,如同在所有其他已测试的物种中一样,当引发正常和免疫淋巴细胞反应时,供体淋巴细胞与之相互作用的唯一重要细胞抗原是对辐射敏感的白细胞。皮肤的组成细胞并不重要。(a) 受辐照实验对象中这些反应的强度取决于外周白细胞浓度。当该浓度降至某个阈值以下时,就无法引发反应。(b) 如果在接种前将具有自身遗传组成的正常淋巴细胞作为“补充抗原”与假定的攻击性供体细胞混合,高度白细胞减少的动物能够产生免疫淋巴细胞转移(ILT)反应。(c) 血液中含有F(1)杂种白细胞的辐射嵌合13号品系动物,当用13号品系抗2号淋巴结细胞进行皮内攻击时,会产生典型的ILT反应。如果在24小时后给2号品系动物皮内注射13号品系淋巴细胞,那么将其暴露于600伦琴的辐射剂量下并不会阻止它们被主动免疫。然而,这种由宿主产生迟发型超敏反应的能力所显示的致敏作用,会随着白细胞减少的进展而减弱。基于这一发现及其他研究结果,可以认为预先受辐照宿主中NLT反应的爆发阶段主要是宿主对转移的外来细胞敏感性的一种表现。在本研究过程中还出现了两个意外发现:(a) F(1)杂种动物在皮内接种亲本品系淋巴细胞或由它们制备的抗原提取物后,出现了似乎强烈的迟发型超敏反应。(b) 如果事先通过皮内注射淋巴细胞使13号品系豚鼠对2号品系组织抗原致敏,然后静脉注射2号品系抗原提取物,相当一部分动物会在部分或所有已愈合的皮肤接种部位出现严重的迟发性坏死反应,即回忆性皮疹。