Lugo J P, Krishnan S N, Sailor R D, Rothenberg E V
Proc Natl Acad Sci U S A. 1986 Mar;83(6):1862-6. doi: 10.1073/pnas.83.6.1862.
T-cell precursors were stimulated with a conventional T-cell mitogen or with the calcium ionophore A23187 in order to determine whether pre-T cells acquire the ability to produce interleukin 2 (IL-2) before they acquire the ability to respond to antigen or mitogenic lectins. Immature T cells were obtained by eliminating mouse thymocytes that expressed the Lyt2 and L3T4 cell surface proteins. The remaining Lyt2-, L3T4- cells were stimulated for IL-2 production by using concanavalin A (Con A) or A23187, together with phorbol 12-myristate 13-acetate (PMA). We found that these "double-negative" thymocytes were unresponsive to Con A plus PMA but produced substantial amounts of IL-2 when stimulated with A23187 plus PMA. In contrast, both stimulation regimens induced more mature T-lymphocyte populations to produce IL-2. This implies that developing T cells acquire the ability to make IL-2 upon induction before they acquire the ability to be triggered by Con A. Day-15 fetal and cortical thymocytes were also tested for their ability to make IL-2. Both populations failed to synthesize this growth factor, even when stimulated with A23187 and PMA. For cortical thymocytes, this result, together with the finding that A23187 plus PMA fails to activate these cells, suggests that this population is immunologically inert rather than immature. On the other hand, the inability of day-15 fetal thymocytes to produce IL-2 indicates that these T-cell precursors are developmentally distinct from adult Lyt2-, L3T4- thymocytes, which they phenotypically resemble.
用传统的T细胞有丝分裂原或钙离子载体A23187刺激T细胞前体,以确定前T细胞在获得对抗原或促有丝分裂凝集素的反应能力之前是否获得产生白细胞介素2(IL-2)的能力。通过去除表达Lyt2和L3T4细胞表面蛋白的小鼠胸腺细胞获得未成熟T细胞。使用伴刀豆球蛋白A(Con A)或A23187以及佛波醇12-肉豆蔻酸酯13-乙酸酯(PMA)刺激剩余的Lyt2-、L3T4-细胞以产生IL-2。我们发现这些“双阴性”胸腺细胞对Con A加PMA无反应,但在用A23187加PMA刺激时产生大量IL-2。相比之下,两种刺激方案均诱导更成熟的T淋巴细胞群体产生IL-2。这意味着发育中的T细胞在获得被Con A触发的能力之前,在诱导时就获得了产生IL-2的能力。还测试了第15天的胎儿胸腺细胞和皮质胸腺细胞产生IL-2的能力。即使在用A23187和PMA刺激时,这两种细胞群体均未能合成这种生长因子。对于皮质胸腺细胞,这一结果以及A23187加PMA未能激活这些细胞的发现表明,该细胞群体在免疫上是惰性的而非未成熟的。另一方面,第15天的胎儿胸腺细胞无法产生IL-2,这表明这些T细胞前体在发育上与成年Lyt2-、L3T4-胸腺细胞不同,尽管它们在表型上相似。