Lichtman A H, Chin J, Schmidt J A, Abbas A K
Department of Pathology, Brigham and Women's Hospital, Boston, MA.
Proc Natl Acad Sci U S A. 1988 Dec;85(24):9699-703. doi: 10.1073/pnas.85.24.9699.
The activation of T lymphocytes requires their stimulation via clonotypic antigen receptors as well as nonantigen-specific costimulators, the best defined of which is the cytokine interleukin 1 (IL-1). Recent studies have shown that murine CD4+ helper T lymphocytes consist of two nonoverlapping subsets that selectively utilize interleukin 2 (IL-2) or interleukin 4 as their autocrine growth factors and are called Th1 and Th2 cells, respectively. We now show that IL-1 functions as a costimulator for the proliferation of Th2 but not of Th1 clones and only Th2 cells express high-affinity receptors for IL-1. Secretion of autocrine growth-promoting lymphokines by Th1 and Th2 cells occurs after stimulation via the antigen receptor-CD3 complex and is neither dependent on nor affected by IL-1. These findings suggest that the activation of T lymphocytes can be divided into two stages, lymphokine secretion and proliferation, and only proliferation requires costimulators such as IL-1. Moreover, the prevailing view that IL-1 functions as a costimulator by inducing secretion of IL-2 or expression of IL-2 receptors may not be generally applicable, because IL-2-producing Th1 clones do not express receptors for IL-1 and are insensitive to this cytokine.
T淋巴细胞的激活需要通过克隆型抗原受体以及非抗原特异性共刺激分子对其进行刺激,其中研究最为透彻的是细胞因子白细胞介素1(IL-1)。最近的研究表明,小鼠CD4+辅助性T淋巴细胞由两个不重叠的亚群组成,它们分别选择性地利用白细胞介素2(IL-2)或白细胞介素4作为自分泌生长因子,分别称为Th1细胞和Th2细胞。我们现在发现,IL-1作为Th2克隆而非Th1克隆增殖的共刺激分子,只有Th2细胞表达IL-1的高亲和力受体。Th1细胞和Th2细胞通过抗原受体-CD3复合物刺激后分泌自分泌促生长淋巴因子,且该过程既不依赖于IL-1,也不受其影响。这些发现表明,T淋巴细胞的激活可分为两个阶段,即淋巴因子分泌和增殖,只有增殖需要诸如IL-1这样的共刺激分子。此外,普遍认为IL-1通过诱导IL-2分泌或IL-2受体表达而发挥共刺激分子作用的观点可能并不普遍适用,因为产生IL-2的Th1克隆不表达IL-1受体,且对该细胞因子不敏感。