Guéry J C, Ria F, Galbiati F, Adorini L
Roche Milano Ricerche, Italy.
Eur J Immunol. 1997 Jul;27(7):1632-9. doi: 10.1002/eji.1830270707.
Interleukin-12 is a key regulatory cytokine produced by antigen-presenting cells (APC) which drives the development of interferon-gamma (IFN-gamma)-producing cells and promotes cell-mediated immunity. Following subcutaneous immunization with protein antigen in adjuvant, dendritic cells (DC) but not small nor large B cells in immune lymph nodes express antigenic complexes and secrete substantial amounts of bioactive IL-12 p75 upon antigen-specific interaction with T cells. We have analyzed secretion of IL-12 p40 and p75 by cell populations enriched in DC, macrophages or B cells in response to nonspecific stimulation or to interaction with antigen-specific CD4+ cells. These APC populations do not produce IL-12 constitutively but, upon stimulation with heat-fixed Staphylococcus aureus and IFN-gamma, IL-12 p40 and p75 are secreted by DC and macrophages, whereas B cells fail to produce IL-12. B cells also fail to secrete IL-12 in response to stimulation with LPS and IFN-gamma. Co-culture with CD4+ T hybridoma cells and antigen induces IL-12 secretion by DC. Up-regulation of IL-12 secretion by interaction with antigen-specific CD4+ T cells is abrogated by anti-class II monoclonal antibodies (mAb), by soluble CD40 molecules and by anti-CD40 ligand mAb, demonstrating a positive feedback between T cells and DC mediated by TCR-peptide/class II and by CD40-CD40 ligand interactions. Expression of class II and CD40 molecules is comparable in B cells and DC, and both APC types activate CD4+ T cells. Yet, even upon interaction with antigen-specific T cells, B cells fail to secrete IL-12. The capacity of B cells to present antigen but not to secrete IL-12 may explain their propensity to selectively drive T helper type 2 cell development.
白细胞介素-12是一种由抗原呈递细胞（APC）产生的关键调节性细胞因子，它驱动产生干扰素-γ（IFN-γ）的细胞的发育并促进细胞介导的免疫。在用佐剂中的蛋白质抗原进行皮下免疫后，免疫淋巴结中的树突状细胞（DC）而非小B细胞或大B细胞表达抗原复合物，并在与T细胞发生抗原特异性相互作用时分泌大量生物活性白细胞介素-12 p75。我们分析了富含DC、巨噬细胞或B细胞的细胞群体在非特异性刺激或与抗原特异性CD4⁺细胞相互作用时白细胞介素-12 p40和p75的分泌情况。这些APC群体不会组成性地产生白细胞介素-12，但在用热固定的金黄色葡萄球菌和IFN-γ刺激后，DC和巨噬细胞会分泌白细胞介素-12 p40和p75，而B细胞则无法产生白细胞介素-12。B细胞在受到LPS和IFN-γ刺激时也无法分泌白细胞介素-12。与CD4⁺T杂交瘤细胞和抗原共培养可诱导DC分泌白细胞介素-12。与抗原特异性CD4⁺T细胞相互作用导致的白细胞介素-12分泌上调被抗II类单克隆抗体（mAb）、可溶性CD40分子和抗CD40配体mAb所消除，这表明T细胞和DC之间由TCR-肽/II类和CD40-CD40配体相互作用介导的正反馈。II类和CD40分子在B细胞和DC中的表达相当，并且这两种APC类型都能激活CD4⁺T细胞。然而，即使与抗原特异性T细胞相互作用，B细胞也无法分泌白细胞介素-12。B细胞呈递抗原但不分泌白细胞介素-12的能力可能解释了它们选择性驱动2型辅助性T细胞发育的倾向。
