Interleukin-12 (IL-12)-driven alloimmune responses in vitro and in vivo: requirement for beta1 subunit of the IL-12 receptor.
Interleukin-12 (IL-12)-driven alloimmune responses in vitro and in vivo: requirement for beta1 subunit of the IL-12 receptor.
复制标题
白细胞介素 12 (IL-12) 驱动的体外和体内同种免疫反应：对 IL-12 受体 β1 亚基的需求。
DOI：
10.1097/00007890-199906150-00011
复制
发表时间：
1999
期刊：
影响因子：
6.2
通讯作者：
Bishop,DK
中科院分区：
文献类型：
--
作者：
Piccotti,JR;Li,K;Chan,SY;Eichwald,EJ;Bishop,DK
背景：白细胞介素12（IL-12）通过与T细胞和自然杀伤细胞上的高亲和力受体结合来介导其生物学活性。虽然重点放在IL-12生物活性中对IL-12 R β2的需求上，但IL-12 R β1的作用还不太清楚。本研究探讨外源性IL-12对同种异体抗原特异性免疫应答的影响，并确定IL-12介导的同种异体免疫应答中IL-12 R β1的需求。此外，测定了添加IL-12的混合淋巴细胞培养物（MLC）中IFN-γ的产生，以评估IL-12对体外Th 1功能的影响。IL-12 R β1（IL-12 R β1−/−）缺陷的小鼠用于确定IL-12驱动的同种异体免疫应答中对该受体组分的需求。结果：在由野生型脾细胞组成的MLC中加入IL-12可增强同种异体抗原特异性增殖应答和Th 1发育。相比之下，IL-12并没有改变IL-12 R β1−/− MLC中的这些体外免疫参数。用IL-12治疗野生型心脏移植物受体导致高浓度的血清干扰素-γ（IFN-γ）和体外再刺激后受体脾细胞产生的IFN-γ增加10倍。然而，这种爆发性Th 1反应并没有加速同种异体移植排斥反应。重要的是，IL-12对血清IFN-γ或IL-12 R β1−/−受体体内Th 1的启动没有影响。最后，管理IL-12 WT同种异体移植物受体导致双峰同种抗体反应：抗体的产生被抑制在高剂量的IL-12，并在较低的doses.Conclusions增强。IL-12显着增强同种异体抗原特异性免疫功能，但是，这些夸大的Th 1驱动的反应并不最终加速同种异体移植物排斥反应。此外，这些数据表明，IL-12 R β1对于外源性IL-12增强体外和体内同种免疫应答是必需的。
Background.Interleukin-12 (IL-12) mediates its biologic activities via binding high-affinity receptors on T and natural killer cells. Although emphasis has been placed on the requirement for IL-12Rβ2 in IL-12 bioactivity, the role of IL-12Rβ1 is less well defined. The current study evaluated the effects of exogenous IL-12 on alloantigen-specific immune responses and determined the requirement for IL-12Rβ1 in IL-12-mediated alloimmunity.Methods.The mouse heterotopic cardiac transplant model was employed to evaluate the effects of IL-12 on alloantigen-specific immune responses in vivo. In addition, IFN-γ production in mixed lymphocyte cultures (MLC) supplemented with IL-12 was measured to assess the effects of IL-12 on Th1 function in vitro. Mice deficient in IL-12Rβ1 (IL-12Rβ1−/−) were used to determine the requirement for this receptor component in IL-12-driven alloimmune responses.Results.Addition of IL-12 to MLC consisting of wild-type splenocytes enhanced alloantigen-specific proliferative responses and Th1 development. In contrast, IL-12 did not alter these in vitro immune parameters in IL-12Rβ1−/− MLC. Treatment of wild-type cardiac allograft recipients with IL-12 resulted in high concentrations of serum interferon-γ (IFN-γ) and a 10-fold increase in IFN-γ production by recipient splenocytes after restimulation in vitro. However, this fulminate Th1 response did not accelerate allograft rejection. Importantly, IL-12 had no effect on serum IFN-γ or in vivo priming of Th1 in IL-12Rβ1−/− recipients. Finally, administration of IL-12 to WT allograft recipients resulted in a bimodal alloantibody response: antibody production was suppressed at high doses of IL-12, and enhanced at lower doses.Conclusions.IL-12 markedly enhances alloantigen-specific immune function; however, these exaggerated Th1-driven responses do not culminate in accelerated allograft rejection. Further, these data indicate that IL-12Rβ1 is essential for the enhancement of both in vitro and in vivo alloimmune responses by exogenous IL-12.