Expression of receptors for interleukin 2: Role in the commitment of T lymphocytes to proliferate.
Expression of receptors for interleukin 2: Role in the commitment of T lymphocytes to proliferate.
复制标题
白细胞介素 2 受体的表达：在 T 淋巴细胞增殖中的作用。
作者：
S. Lipkowitz;W. Greene;A. Rubin;A. Novogrodsky;K. Stenzel
我们研究了IL - 2和IL - 2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。用这些含醛巨噬细胞培养的T淋巴细胞在激活2至4小时后就对IL - 2产生反应，并在激活18至24小时后表现出最大的IL - 2反应。IL - 2受体的早期表达也通过单克隆抗IL - 2受体抗体（anti-Tac）与活化的T淋巴细胞的直接结合而得到证实。用nago处理的巨噬细胞培养的T淋巴细胞产生IL - 2的过程与IL - 2受体在T淋巴细胞上的诱导密切相关。IL - 2在激活4 - 8小时后开始产生，在大约18小时时达到峰值。尽管IL - 2的产生严格依赖于辅助细胞的功能，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IL - 2受体并早期产生IL - 2，但直到与nago处理的巨噬细胞孵育超过24小时后，T淋巴细胞才会在没有IL - 2的情况下增殖。激活24小时后，细胞的增殖能力增强，直到激活40多小时后，细胞在IL - 2存在或不存在的情况下都能很好地增殖。通过使用抗tac抗体阻断IL 2受体，干扰IL 2与其受体的结合，可以抑制携带IL 2受体的未提交T淋巴细胞的增殖。相比之下，致力于增殖的T淋巴细胞的增殖不受IL 2受体阻断和抗tac抗体的影响。综上所述，这些数据表明T淋巴细胞的激活有三个阶段。第一阶段需要有丝分裂原（或抗原）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，但它们可能不是IL - 2受体表达所必需的。第二阶段是依赖IL - 2的阶段，需要IL - 2与新表达的IL - 2受体相互作用。第三阶段是激活的T淋巴细胞增殖的承诺，不依赖于有丝分裂原和白细胞介素2。
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.