Wijesuriya R, Maruo S, Zou J P, Ogawa M, Umehara K, Yamashita M, Ono S, Fujiwara H, Hamaoka T
Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Int Immunol. 1998 Aug;10(8):1057-65. doi: 10.1093/intimm/10.8.1057.
Unfractionated spleen cells taken from tumor-bearing mice contained tumor-primed T cells which produced lymphokines such as IFN-gamma and IL-2 through collaboration with antigen-presenting cells (APC) binding tumor antigens when cultured in vitro. Here, we investigated the regulatory mechanisms underlying IFN-gamma production by T-APC interactions. Elimination of B cells from a splenic population of tumor-bearing mice resulted in enhanced IFN-gamma production. Adding B cells back into cultures down-regulated IFN-gamma production to almost the same levels as those induced by unfractionated spleen cells. IL-2 production was not enhanced by B cell depletion, but rather was significantly suppressed. IFN-gamma-selective up-regulation was due to an enhancement of IL-12 production because IL-12 was detected in B cell-depleted cultures and enhanced IFN-gamma production was prevented by addition of anti-IL-12 mAb or anti-CD40 ligand (CD40L) mAb capable of inhibiting CD40L-induced IL-12 production. These results indicate that B cells interfere with IFN-gamma production induced through interactions between anti-tumor T cells and APC, and this suppressive effect is based on the capacity of CD40+ B cells to down-regulate the CD40L-induced IL-12 production by APC.
取自荷瘤小鼠的未分离脾细胞含有经肿瘤致敏的T细胞，当在体外培养时，这些T细胞通过与结合肿瘤抗原的抗原呈递细胞（APC）协作产生诸如干扰素-γ（IFN-γ）和白细胞介素-2（IL-2）等淋巴因子。在此，我们研究了T细胞与APC相互作用介导IFN-γ产生的调控机制。从荷瘤小鼠的脾细胞群体中去除B细胞导致IFN-γ产生增强。将B细胞重新加入培养物中可将IFN-γ产生下调至与未分离脾细胞诱导的水平几乎相同。B细胞耗竭并未增强IL-2的产生，反而显著抑制了IL-2的产生。IFN-γ的选择性上调是由于IL-12产生增加，因为在B细胞耗竭的培养物中检测到了IL-12，并且加入能够抑制CD40L诱导的IL-12产生的抗IL-12单克隆抗体或抗CD40配体（CD40L）单克隆抗体可阻止IFN-γ产生的增强。这些结果表明，B细胞干扰通过抗肿瘤T细胞与APC之间的相互作用诱导的IFN-γ产生，并且这种抑制作用基于CD40⁺B细胞下调APC的CD40L诱导的IL-12产生的能力。
