Eynon E E, Parker D C
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01655.
J Immunol. 1993 Sep 15;151(6):2958-64.
We have shown that a foreign protein Ag (the F(ab) fragment of rabbit IgG) becomes a particularly effective tolerogen when it is targeted to B lymphocytes in vivo. This is done by injecting the Ag intravenously into mice in the form of the F(ab) fragment of rabbit anti-mouse IgD antibody (F(ab)) rabbit anti-delta). Our hypothesis is that resting B cells are tolerogenic APC for CD4+ T cells in unprimed animals, and induce Ag-specific nonresponsiveness in the Th cell compartment by presenting Ag without appropriate costimulatory signals. In this report, we find that Ag-activated T cells appear to be resistant to tolerance induction, because F(ab) rabbit anti-delta given 5 days after challenge with rabbit F(ab) in alum adjuvant has little or no effect of the subsequent antibody response. Tolerance also fails in this model when B cells are activated independently of Ag by simultaneous injection of activating concentrations of divalent, IgG mouse anti-delta at the same time as F(ab) rabbit anti-delta. Finally, nonresponsiveness in the T cell compartment is not limited to a lesion in T cell help for the antibody response, because T cells from mice treated with F(ab) rabbit anti-delta and then primed with rabbit F(ab) fragments in CFA show reduced T cell proliferation and IL-2 production when restimulated with Ag in vitro.
我们已经表明，一种外源蛋白抗原（兔IgG的F(ab)片段）在体内靶向B淋巴细胞时会成为一种特别有效的耐受原。这是通过将抗原以兔抗小鼠IgD抗体的F(ab)片段（F(ab)兔抗δ）的形式静脉注射到小鼠体内来实现的。我们的假设是，静息B细胞在未致敏动物中是CD4+T细胞的致耐受性抗原呈递细胞，并通过在没有适当共刺激信号的情况下呈递抗原来诱导Th细胞区室中的抗原特异性无反应性。在本报告中，我们发现抗原激活的T细胞似乎对耐受诱导具有抗性，因为在用明矾佐剂中的兔F(ab)攻击后5天给予F(ab)兔抗δ对随后的抗体反应几乎没有影响。当B细胞通过与F(ab)兔抗δ同时注射激活浓度的二价IgG小鼠抗δ而独立于抗原被激活时，该模型中的耐受性也会失败。最后，T细胞区室中的无反应性并不局限于抗体反应中T细胞辅助的损伤，因为用F(ab)兔抗δ处理然后在CFA中用兔F(ab)片段致敏的小鼠的T细胞在体外用抗原重新刺激时显示出T细胞增殖和IL-2产生减少。
