Langerhans cell migration in mice requires intact type I interleukin 1 receptor (IL-1RI) function
Langerhans cell migration in mice requires intact type I interleukin 1 receptor (IL-1RI) function
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DOI：
10.1007/s004030050422
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发表时间：
1999-06-01
影响因子：
3
通讯作者：
Kimber, I
中科院分区：
文献类型：
--
作者：
Cumberbatch, M;Dearman, RJ;Kimber, I
在初步实验中，研究了这些抗体对局部暴露于恶唑酮小鼠引流淋巴结中DC积累的影响。各组BALB/c株小鼠双耳廓皮内注射大鼠抗小鼠IL-1R抗体或等量对照大鼠IgG。90分钟后，小鼠局部暴露于恶唑酮。对照组（未成熟）小鼠未经治疗。18小时后切除引流的耳穴淋巴结，使用先前描述的方法（Cumberbatch and Kimber 1992）通过对淋巴结细胞中富含DC的部分进行直接形态学检查来评估每个淋巴结的DC频率。图1总结了两个独立实验的结果。发现恶唑酮在引流淋巴结中诱导大量DC积聚。先前用抗il - 1ri抗体局部治疗小鼠，对DC积累有非常明显的抑制作用，而抗il - 1rii抗体几乎没有作用（图1）。局部注射抗体或对照IgG对静息或对照（丙酮：橄榄油处理）淋巴结DC数均无影响（数据未显示）。在之前的实验中，我们已经证明LC需要TNF-α和IL-1β的信号来迁移（Cumberbatch et al. 1997b）。因此，发现由过敏原或TNF-α引起的LC动员依赖于IL-1β的局部可用性。为了进一步研究这一要求，我们现在研究了抗il - 1r抗体对皮内注射同源重组TNF-α诱导的DC积累的刺激的影响。如上所述，在注射前90分钟，在牛血清白蛋白（BSA）中悬浮的TNF-α的同一部位皮下注射抗il - 1r抗体或对照免疫球蛋白。对照组（未成熟）小鼠未经治疗。暴露于TNF-α后4小时切除引流耳淋巴结，DC频率如上所述。两个独立的实验如图2所示。在这两种情况下，TNF-α引起引流淋巴结内DC数量的大幅增加，而这种增加在很大程度上或完全被先前暴露于抗il - 1ri的小鼠所抑制。相比之下，抗il - 1rii抗体要么对DC积累没有影响，要么只引起适度的减少（图2）。单独皮内给药BSA或在同一部位预处理抗il - 1r抗体，对DC积累没有影响（数据未显示）。总的来说，这些数据表明，局部暴露于接触性过敏原或TNF-α诱导的DC积累的完整性被抗il - 1ri严重破坏，而不是被抗il - 1rii阻断抗体破坏。在上述实验中，对照大鼠IgG单独对DC积累没有任何影响。最后进行了一系列实验，以直接检查这些抗体对LC从表皮迁移的影响。为此，LC的迁移是通过皮内注射同源重组TNF-α而不是过敏原来刺激的。我们之前已经证明，TNF-α刺激一定比例的LC从表皮快速迁移（30分钟内）；与过敏原一样，反应也取决于IL-1β的可用性（Cumberbatch et al. 1994,1997b）。小鼠在接受第二次皮内注射牛血清白蛋白中的TNF-α或单独的牛血清白蛋白之前90分钟，在同一部位皮内注射抗il - 1r抗体或对照免疫球蛋白到双耳廓。再过30分钟，去耳，MHC II类(Ia)+ LC的频率…
In preliminary experiments the ability of these antibodies to influence DC accumulation in draining lymph nodes induced by topical exposure of mice to oxazolone was investigated. Groups of BALB/c strain mice received intradermal injections into both ear pinnae of rat antimouse IL-1R antibodies, or of the same amount of control rat IgG. Mice were exposed topically to oxazolone 90 min later. Control (naive) mice were untreated. Draining auricular lymph nodes were excised 18 h later and the frequency of DC per node assessed by direct morphological examination of DC-enriched fractions of lymph node cells using a method described previously (Cumberbatch and Kimber 1992). Figure 1 summarizes the results obtained in two independent experiments. Oxazolone was found to induce a substantial accumulation of DC in draining lymph nodes. Prior local treatment of mice with anti-IL-1RI antibody resulted in a very substantial inhibition of DC accumulation, whereas anti-IL-1RII antibody had little effect (Fig. 1). Local administration of antibodies, or control IgG, was without effect on either resting or control (acetone: olive oil-treated) lymph node DC numbers (data not shown). In previous experiments we have demonstrated that LC require signals from both TNF-α and IL-1β for migration (Cumberbatch et al. 1997b). Thus, LC mobilization provoked by either allergen or TNF-α was found to be dependent upon the local availability of IL-1β. To investigate this requirement further we have now examined the influence of anti-IL-1R antibodies on the stimulation of DC accumulation induced by the intradermal injection of homologous recombinant TNF-α. Groups of mice were treated intradermally with anti-IL-1R antibodies or control immunoglobulin, as described above, 90 min prior to injection at the same site of TNF-α suspended in bovine serum albumin (BSA). Control (naive) mice were untreated. Draining auricular lymph nodes were excised 4 h following exposure to TNF-α and the frequency of DC determined as above. Two separate experiments are illustrated in Fig. 2. In both instances TNF-α caused a substantial increase in the number of DC within draining nodes which was largely or completely inhibited by prior exposure of mice to anti-IL-1RI. In contrast, anti-IL-1RII antibody was either without effect on DC accumulation or caused only a modest reduction (Fig. 2). Intradermal administration of BSA alone or pretreatment with anti-IL-1R antibodies at the same site, had no effect on DC accumulation (data not shown). Collectively, these data demonstrate that the integrity of DC accumulation induced in mice by local exposure to either a contact allergen or TNF-α is compromised very substantially by anti-IL-1RI, but not by anti-IL-1RII, blocking antibodies. In none of the experiments described above did control rat IgG alone have any effect on DC accumulation. A final series of experiments was performed to examine directly the influence of these antibodies on LC migration from the epidermis. For this purpose LC migration was stimulated by the intradermal injection of homologous recombinant TNF-α rather than allergen. We have shown previously that TNF-α stimulates the very rapid migration (within 30 min) of a proportion of LC from the epidermis; a response, that like allergen, is dependent upon the availability of IL-1β (Cumberbatch et al. 1994, 1997b). Mice received intradermal injections of anti-IL-1R antibodies, or of control immunoglobulin, into both ear pinnae, 90 min prior to receipt at the same site of a second intradermal injection of either TNF-α in BSA, or of BSA alone. After a further 30 min, ears were removed and the frequency of MHC class II (Ia)+ LC …