Sanderson C J
National Institute for Medical Research, London, England.
Immunol Ser. 1990;49:231-56.
The development of eosinophilia has an interesting biological specificity, in that the numbers of eosinophils can increase from a normal paucity to very high levels, without a concomitant increase in other leukocytes. This suggests a unique controlling mechanism. Although IL-3, GM-CSF, and IL-5 all induce eosinophil differentiation, IL-5 is the only identified cytokine specific for the eosinophil lineage. This together with the fact that IL-5 can be detected in the serum of mice with eosinophilia suggests that it may be a critical controlling factor. The mechanism of this control is not yet clear. It appears that a high proportion of T-cell clones produce IL-5, even when isolated using antigens that do not induce eosinophilia. If IL-5 is produced in response to all antigens, what is the basis for the biological specificity of eosinophilia? It is possible that the production of lymphokines by isolated T-cell clones does not reflect the true biological situation, because there may be a selection process in the isolation of T cells that is not yet understood. In addition, IL-5 appears not to stimulate the production of precursors committed to the eosinophil lineage, at least in vitro. Thus, it would seem likely that other controlling mechanisms exist to generate the precursors. Attempts to study this stage of eosinophil production are difficult to interpret. The experiments are technically difficult, and conflicting results have been reported. Interleukin-3 and GM-CSF appear to have this activity in vitro, but it is not clear how these factors could be active in the production of eosinophil precursors without also inducing increases in other leukocyte types, particularly neutrophils. Another intriguing aspect of the biology of IL-5 is the activity on other cell types, particularly B cells in the mouse. This activity as a murine BCGF precedes the identification of IL-5 as an eosinophil differentiation factor, and has been studied in considerable detail for many years. However, if IL-5 is important in the production of antibody, why are eosinophils not seen in all immune responses? An important insight into this problem has come from the observation that human IL-5 has no analogous activity on human B cells. If IL-5 is not active on human B cells, it raises questions about the biological role of IL-5 as a BCGF in the mouse.(ABSTRACT TRUNCATED AT 400 WORDS)
嗜酸性粒细胞增多的发展具有有趣的生物学特异性,即嗜酸性粒细胞数量可从正常的少量增加到非常高的水平,而其他白细胞却没有相应增加。这表明存在一种独特的控制机制。尽管白细胞介素-3(IL-3)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-5(IL-5)都能诱导嗜酸性粒细胞分化,但IL-5是唯一已确定的对嗜酸性粒细胞谱系具有特异性的细胞因子。这一点连同在嗜酸性粒细胞增多的小鼠血清中可检测到IL-5这一事实,表明它可能是一个关键的控制因素。这种控制机制尚不清楚。似乎即使使用不诱导嗜酸性粒细胞增多的抗原进行分离,仍有很大比例的T细胞克隆会产生IL-5。如果IL-5是对所有抗原都产生反应,那么嗜酸性粒细胞增多的生物学特异性的基础是什么呢?有可能分离出的T细胞克隆产生淋巴因子的情况并不能反映真实的生物学状况,因为在T细胞分离过程中可能存在一个尚未被理解的选择过程。此外,至少在体外,IL-5似乎不会刺激嗜酸性粒细胞谱系的前体细胞的产生。因此,似乎很可能存在其他控制机制来产生前体细胞。研究嗜酸性粒细胞产生的这个阶段的尝试很难解释。这些实验在技术上很困难,并且已经报道了相互矛盾的结果。IL-3和GM-CSF在体外似乎具有这种活性,但尚不清楚这些因子在不诱导其他白细胞类型(特别是中性粒细胞)增加的情况下,如何能在嗜酸性粒细胞前体细胞的产生中发挥作用。IL-5生物学的另一个有趣方面是其对其他细胞类型的活性,特别是对小鼠B细胞的活性。IL-5作为小鼠B细胞生长因子(BCGF)的这种活性在其被鉴定为嗜酸性粒细胞分化因子之前就已被发现,并且已经进行了多年的详细研究。然而,如果IL-5在抗体产生中很重要,为什么在所有免疫反应中都看不到嗜酸性粒细胞呢?对这个问题的一个重要见解来自于观察到人类IL-5对人类B细胞没有类似的活性。如果IL-5对人类B细胞没有活性,这就引发了关于IL-5作为小鼠BCGF的生物学作用的疑问。(摘要截选至400字)