Boucher L M, Wiegmann K, Fütterer A, Pfeffer K, Machleidt T, Schütze S, Mak T W, Krönke M
Institute of Medical Microbiology, Technical University of Munich, Germany.
J Exp Med. 1995 Jun 1;181(6):2059-68. doi: 10.1084/jem.181.6.2059.
T cell receptor recognition of antigen can lead either to T lymphocyte differentiation and proliferation or to a state of unresponsiveness, which is dependent on whether appropriate costimulatory signals are provided to the mature T cell. We have investigated a novel intracellular signaling pathway provided by the costimulatory molecule CD28. CD28 engagement triggers the activation of an acidic sphingomyelinase (A-SMase), which results in the generation of ceramide, an important lipid messenger intermediate. A-SMase activation by CD28 occurred in resting as well as in activated primary T cells or leukemic Jurkat cells. In contrast, ligation of either CD3 or CD2 did not result in A-SMase activation. Overexpression of recombinant A-SMase in Jurkat T cells substituted for CD28 with regard to nuclear factor-kB activation. These data suggest that CD28 provides an important costimulatory signal by activation of an acidic sphingomyelinase pathway.
T细胞受体对抗原的识别可导致T淋巴细胞分化和增殖，也可导致无反应状态，这取决于是否向成熟T细胞提供适当的共刺激信号。我们研究了共刺激分子CD28提供的一种新型细胞内信号通路。CD28的结合触发酸性鞘磷脂酶（A-SMase）的激活，这导致神经酰胺的生成，神经酰胺是一种重要的脂质信使中间体。CD28对A-SMase的激活发生在静止的以及活化的原代T细胞或白血病Jurkat细胞中。相比之下，CD3或CD2的连接均不会导致A-SMase激活。重组A-SMase在Jurkat T细胞中的过表达在核因子-κB激活方面替代了CD28。这些数据表明，CD28通过激活酸性鞘磷脂酶途径提供重要的共刺激信号。
