Reyes V E, Klimpel K D, Klimpel G R
J Immunol. 1985 May;134(5):3137-41.
We have previously reported that mouse bone marrow cells produce high levels of interferon-alpha/beta (IFN-alpha/beta) after 5 to 6 days of in vitro culture with irradiated allogenic spleen cells. The current study was initiated to determine whether or not T cells are important for alloantigen-induced IFN-alpha/beta production by mouse bone marrow cells. Bone marrow cells and spleen cells were obtained from C57BL/6 mice. These cells were treated with different monoclonal antisera and complement, and then were cultured 5 to 6 days with irradiated DBA spleen cells. The results from these experiments indicated that optimal IFN-alpha/beta production by alloantigen-stimulated bone marrow cells required Lyt-1+2+ T cells. In addition, when bone marrow cells obtained from nu/nu B10 mice were cultured with alloantigen, only low levels of IFN were produced when compared with IFN production by bone marrow cells obtained from normal littermate B10 mice. The addition of nylon wool-enriched splenic T cells to cultures containing bone marrow cells and alloantigen resulted in an augmentation of IFN-alpha/beta production by three-fold to fivefold. Furthermore, bone marrow cells obtained from alloantigen-immunized mice produced much higher levels of IFN-alpha/beta and in a shorter period of time (2 to 3 days) when compared with bone marrow cells obtained from control or non-immunized mice. Cyclosporin A (CsA) has been shown to inhibit predominantly T cell-dependent responses. The effect of CsA on IFN production by alloantigen-stimulated bone marrow and spleen cells was investigated. The addition of CsA at concentrations as low as 0.1 micrograms/ml inhibited not only IFN-gamma production by alloantigen-stimulated spleen cells, but also IFN-alpha/beta production by alloantigen-stimulated bone marrow cells. In contrast, IFN-alpha/beta production by Newcastle disease virus-infected spleen cells, bone marrow cells, or L cells was not inhibited by the addition of CsA (1 microgram/ml). Thus, the ability of bone marrow cells to produce high levels of IFN-alpha/beta after in vitro culture with alloantigen is dependent upon T cells resident in the bone marrow. IFN-alpha/beta production by alloantigen-stimulated bone marrow cells may play a major role in the pathogenesis associated with graft-vs-host disease and in T cell regulation of hematopoiesis.
我们之前曾报道，小鼠骨髓细胞在与经辐照的同种异体脾细胞进行体外培养5至6天后会产生高水平的α/β干扰素（IFN-α/β）。当前的研究旨在确定T细胞对于小鼠骨髓细胞由同种异体抗原诱导产生IFN-α/β是否重要。从C57BL/6小鼠获取骨髓细胞和脾细胞。这些细胞用不同的单克隆抗血清和补体处理，然后与经辐照的DBA脾细胞一起培养5至6天。这些实验的结果表明，同种异体抗原刺激的骨髓细胞产生最佳的IFN-α/β需要Lyt-1 + 2 + T细胞。此外，当将从裸鼠/裸B10小鼠获得的骨髓细胞与同种异体抗原一起培养时，与从正常同窝B10小鼠获得的骨髓细胞产生的IFN相比，仅产生低水平的IFN。向含有骨髓细胞和同种异体抗原的培养物中添加经尼龙毛富集的脾T细胞会导致IFN-α/β的产生增加三至五倍。此外，与从对照或未免疫小鼠获得的骨髓细胞相比，从经同种异体抗原免疫的小鼠获得的骨髓细胞在更短的时间内（2至3天）产生更高水平的IFN-α/β。环孢素A（CsA）已被证明主要抑制T细胞依赖性反应。研究了CsA对同种异体抗原刺激的骨髓细胞和脾细胞产生IFN的影响。添加低至0.1微克/毫升浓度的CsA不仅抑制同种异体抗原刺激的脾细胞产生IFN-γ，还抑制同种异体抗原刺激的骨髓细胞产生IFN-α/β。相反，添加CsA（1微克/毫升）不会抑制新城疫病毒感染的脾细胞、骨髓细胞或L细胞产生IFN-α/β。因此，骨髓细胞在与同种异体抗原进行体外培养后产生高水平IFN-α/β的能力取决于骨髓中驻留的T细胞。同种异体抗原刺激的骨髓细胞产生IFN-α/β可能在与移植物抗宿主病相关的发病机制以及造血的T细胞调节中起主要作用。
