Elson C O, Beagley K W, Sharmanov A T, Fujihashi K, Kiyono H, Tennyson G S, Cong Y, Black C A, Ridwan B W, McGhee J R
Department of Medicine, University of Alabama at Birmingham Medical Center 35294, USA.
J Immunol. 1996 Sep 1;157(5):2174-85.
We report here a murine model for experimental chronic colitis where administration of trinitrobenzene sulfonic acid (TNBS) in 50% ethanol induced inflammation of large intestine in susceptible (C3H/HeJ and BALB/c) but not resistant (C57BL/6 and DBA/2) mouse strains. We queried whether mucosal trinitrophenyl (TNP)-specific B cell responses were induced in mice with TNBS-induced colitis, and if induction of tolerance to TNBS by oral administration of this hapten protected mice from development of colitis. Isotypes and subclasses of polyclonal and TNP-specific Ab-forming cells (AFC) were assessed in mucosal and peripheral lymphoid tissues of C3H/HeJ mice with TNBS-induced colitis. Increased numbers of IgA- and IgG-secreting cells were found in the inflamed colon lamina propria. Inflamed colonic tissue also contained high frequencies of IgG anti-TNP AFC (predominantly of IgG1, IgG2a, and IgG2b subclasses); however, anti-TNP responses in noninflamed mucosal tissues of mice with colitis exhibited dominant IgA and IgM with low IgG anti-TNP responses. CD4+ T cells stimulated with TNP-splenocytes produced more IFN-gamma and less IL-4, suggesting a Th1-type response. Oral administration of TNBS before induction of colitis markedly decreased mucosal anti-TNP responses and completely inhibited anti-TNP IgG2a and IgG2b responses. Control mice did not show inhibition of anti-TNP AFC responses or TNBS-induced colitis. Intracolonic sensitization of susceptible C3H/HeJ mice with TNBS induces a localized IgG anti-TNP B cell response in the inflamed tissue, whereas prior oral administration of TNBS results in unresponsiveness to this agent and protects mice from development of TNBS-induced colitis.
我们在此报告一种用于实验性慢性结肠炎的小鼠模型，其中在50%乙醇中给予三硝基苯磺酸（TNBS）可诱导易感（C3H/HeJ和BALB/c）但非抗性（C57BL/6和DBA/2）小鼠品系的大肠炎症。我们探究了TNBS诱导的结肠炎小鼠是否诱导了黏膜三硝基苯基（TNP）特异性B细胞反应，以及口服该半抗原诱导对TNBS的耐受性是否能保护小鼠免于结肠炎的发展。在患有TNBS诱导的结肠炎的C3H/HeJ小鼠的黏膜和外周淋巴组织中评估了多克隆和TNP特异性抗体形成细胞（AFC）的亚型和亚类。在发炎的结肠固有层中发现分泌IgA和IgG的细胞数量增加。发炎的结肠组织中也含有高频率的IgG抗TNP AFC（主要为IgG1、IgG2a和IgG2b亚类）；然而，结肠炎小鼠未发炎的黏膜组织中的抗TNP反应以IgA和IgM为主，IgG抗TNP反应较低。用TNP - 脾细胞刺激的CD4 + T细胞产生更多的IFN - γ和更少的IL - 4，表明是Th1型反应。在诱导结肠炎之前口服TNBS显著降低了黏膜抗TNP反应，并完全抑制了抗TNP IgG2a和IgG2b反应。对照小鼠未显示抗TNP AFC反应或TNBS诱导的结肠炎受到抑制。用TNBS对易感的C3H/HeJ小鼠进行结肠内致敏可在发炎组织中诱导局部IgG抗TNP B细胞反应，而预先口服TNBS会导致对该试剂无反应，并保护小鼠免于TNBS诱导的结肠炎的发展。
