Davignon J L, Kimoto M, Kindler V, De Kossodo S, Vassalli P, Izui S
Department of Pathology, University of Geneva, Switzerland.
Eur J Immunol. 1988 Sep;18(9):1367-72. doi: 10.1002/eji.1830180910.
Murine spleen and lymph node L3T4+ T cells were found to spontaneously produce high levels of interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in cultures containing 10% fetal calf serum (FCS) in the absence of other stimulation. The IL3 and GM-CSF activities in culture supernatants peake between the fifth and seventh day of culture. The specificity of the bioassays was attested by the use of rabbit anti-IL3 and anti-GM-CSF antibodies, as well as by the detection of a maximal accumulation of IL3 and GM-CSF mRNA on the fourth day. In contrast, no significant activities of IL2, IL4 or interferon-gamma were detected in these culture supernatants. The markedly limited production of IL3 and GM-CSF in cultures performed in 1% autologous normal mouse serum and the inhibitory effect of anti-Ia or anti-L3T4 monoclonal antibody strongly suggest that the selective production of most, if not all IL3 and GM-CSF by L3T4+ T cells is a result of activation of L3T4+ T cells by fetal calf serum. All the strains of mice tested except athymic nude mice produced substantial amounts of IL3 and GM-CSF during the culture. This is in contrast to a previous report (Palacios, Eur. J. Immunol. 1984. 14: 599), indicating that only spleen cells of the MRL strain homozygous for the lpr gene spontaneously release IL3 in cultures. We found that spleen and lymph node cells from MRL/MpJ-lpr/lpr or C57BL/6J-lpr/lpr mice released, in fact, much less IL3 and GM-CSF in cultures. This was, however, due to the high proportion of the peculiar lpr Ly-2-/L3T4-T cells in spleen and lymph nodes, since after depletion of this lpr T cell subset, lymph node cells from C57BL/6J-lpr/lpr mice produced IL3 and GM-CSF at levels comparable to those in C57BL/6J-+/+ mice. These results further support the notion that the lpr Ly-2-/L3T4- T cell subset is immunologically nonfunctional and its accumulation dilutes functional L3T4+ T cells in mice bearing the lpr mutation.
在含有10%胎牛血清（FCS）且无其他刺激的培养物中，发现小鼠脾脏和淋巴结的L3T4 + T细胞能自发产生高水平的白细胞介素3（IL3）和粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）。培养上清液中的IL3和GM - CSF活性在培养的第5天至第7天达到峰值。通过使用兔抗IL3和抗GM - CSF抗体以及在第4天检测到IL3和GM - CSF mRNA的最大积累，证实了生物测定的特异性。相比之下，在这些培养上清液中未检测到IL2、IL4或干扰素 - γ的显著活性。在1%自体正常小鼠血清中进行的培养中IL3和GM - CSF的产生明显受限，以及抗Ia或抗L3T4单克隆抗体的抑制作用强烈表明，L3T4 + T细胞选择性产生大部分（如果不是全部）IL3和GM - CSF是胎牛血清激活L3T4 + T细胞的结果。除无胸腺裸鼠外，所有测试的小鼠品系在培养过程中都产生了大量的IL3和GM - CSF。这与之前的一份报告（Palacios，《欧洲免疫学杂志》1984年。14：599）相反，该报告表明只有纯合lpr基因的MRL品系的脾细胞在培养物中自发释放IL3。我们发现，来自MRL/MpJ - lpr/lpr或C57BL/6J - lpr/lpr小鼠的脾脏和淋巴结细胞在培养物中释放的IL3和GM - CSF实际上要少得多。然而，这是由于脾脏和淋巴结中特殊的lpr Ly - 2 - /L3T4 - T细胞比例很高，因为在去除这个lpr T细胞亚群后，来自C57BL/6J - lpr/lpr小鼠的淋巴结细胞产生IL3和GM - CSF的水平与C57BL/6J - +/+小鼠相当。这些结果进一步支持了这样一种观点，即lpr Ly - 2 - /L3T4 - T细胞亚群在免疫上无功能，其积累稀释了携带lpr突变的小鼠中功能性L3T4 + T细胞。
