Lipkowitz S, Greene W C, Rubin A L, Novogrodsky A, Stenzel K H
J Immunol. 1984 Jan;132(1):31-7.
We examined the role of IL 2 and IL 2 receptors in human T lymphocyte proliferation induced by neuraminidase and galactose oxidase (NAGO)-treated autologous macrophages. T lymphocytes cultured with these aldehyde-bearing macrophages developed responsiveness to IL 2 after as few as 2 to 4 hr of activation and exhibited maximal responsiveness to IL 2 after 18 to 24 hr of activation. This early expression of IL 2 receptors was also shown by the direct binding of a monoclonal anti-IL 2 receptor antibody (anti-Tac) to the activated T lymphocytes. The production of IL 2 by T lymphocytes cultured with NAGO-treated macrophages closely paralleled the induction of IL 2 receptors on the T lymphocytes. IL 2 production began after 4 to 8 hr of activation and peaked at approximately 18 hr. Although the production of IL 2 is strictly dependent upon accessory cell function, the expression of receptors for IL 2 seems to be relatively independent of accessory cells. Despite early expression of receptors for IL 2 and early production of IL 2 by T lymphocytes during activation, T lymphocytes were not committed to proliferate in the absence of IL 2 until more than 24 hr of incubation with NAGO-treated macrophages had elapsed. The commitment to proliferate increased after 24 hr of activation until, after more than 40 hr of activation, the cells proliferated equally well in the presence or absence of IL 2. Proliferation of uncommitted, IL 2 receptor-bearing T lymphocytes was inhibited by interfering with IL 2 binding to its receptor by IL 2 receptor blockade with the anti-Tac antibody. In contrast, proliferation of T lymphocytes committed to proliferate was not affected by IL 2 receptor blockade with the anti-Tac antibody. Taken together, these data suggest three phases of T lymphocyte activation. The first phase requires mitogen (or antigen) to induce expression of IL 2 receptors and production of IL 2 by the T lymphocytes. Accessory cells are strictly required for IL 2 production during this activation phase, but they may not be necessary for expression of IL 2 receptors. The second phase is an IL 2-dependent phase that requires the interaction of IL 2 with the newly expressed IL 2 receptors. The third phase is a commitment of the activated T lymphocytes to proliferate that is independent of both mitogen and IL 2.
我们研究了白细胞介素2（IL 2）及其受体在神经氨酸酶和半乳糖氧化酶（NAGO）处理的自体巨噬细胞诱导的人T淋巴细胞增殖中的作用。与这些带有醛基的巨噬细胞一起培养的T淋巴细胞在激活仅2至4小时后就对IL 2产生反应，并在激活18至24小时后对IL 2表现出最大反应。单克隆抗IL 2受体抗体（抗Tac）与活化的T淋巴细胞的直接结合也显示了IL 2受体的这种早期表达。与NAGO处理的巨噬细胞一起培养的T淋巴细胞产生IL 2的情况与T淋巴细胞上IL 2受体的诱导密切平行。IL 2的产生在激活4至8小时后开始，并在约18小时达到峰值。虽然IL 2的产生严格依赖于辅助细胞功能，但IL 2受体的表达似乎相对独立于辅助细胞。尽管在激活过程中T淋巴细胞早期表达了IL 2受体并早期产生了IL 2，但在与NAGO处理的巨噬细胞孵育超过24小时之前，T淋巴细胞在没有IL 2的情况下不会开始增殖。激活24小时后增殖的倾向增加，直到激活超过40小时后，细胞在有或没有IL 2的情况下增殖情况相同。通过用抗Tac抗体阻断IL 2受体来干扰IL 2与其受体的结合，可抑制未激活的、带有IL 2受体的T淋巴细胞的增殖。相反，已决定增殖的T淋巴细胞的增殖不受抗Tac抗体阻断IL 2受体的影响。综上所述，这些数据提示了T淋巴细胞激活的三个阶段。第一阶段需要有丝分裂原（或抗原）来诱导T淋巴细胞表达IL 2受体并产生IL 2。在这个激活阶段，IL 2的产生严格需要辅助细胞，但它们对于IL 2受体的表达可能不是必需的。第二阶段是IL 2依赖阶段，需要IL 2与新表达的IL 2受体相互作用。第三阶段是活化的T淋巴细胞决定增殖，这一过程独立于有丝分裂原和IL 2。
