Tamma Seetha M Lakshmi, Balan Satya Priya, Chung Ken Wook, Pahwa Savita
Department of Biomedical Sciences, C. W. Post Campus, Long Island University, Brookville, NY 11548, USA.
J Leukoc Biol. 2006 Apr;79(4):876-80. doi: 10.1189/jlb.0905512. Epub 2006 Jan 24.
Costimulatory signals play an important role in the development of T helper cell type 1 (Th1) or Th2 type. Little is known about jacalin plus CD28-mediated signaling and cytokine secretion. In the present study, we analyzed the intracellular signaling events following stimulation of CD4+ T cells with jacalin plus CD28 cross-linking (CD28XL) with anti-CD28 antibody. Our results indicate enhanced phosphorylation of Tec and linker for activation of T cells when compared with stimulation with jacalin alone or CD28XL alone. Stimulation with jacalin or CD28XL appears to be insufficient to induce interleukin (IL)-4 secretion; however, CD28XL followed by stimulation with jacalin resulted in enhanced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and increased secretion of IL-4. However, compared with stimulation with phorbol 12-myristate 13-acetate plus ionomycin, jacalin plus CD28XL resulted in decreased levels of tumor necrosis factor alpha secretion. Addition of p38 inhibitor, SB203580, inhibited p38 phosphorylation and IL-4 secretion. These data suggest that jacalin stimulation alone appears to be insufficient for Th2 development, and addition of CD28 costimulation induced Th2 generation. We propose that jacalin plus CD28XL induces Th2 differentiation via activation of p38 MAPK.
共刺激信号在1型辅助性T细胞(Th1)或2型辅助性T细胞(Th2)的发育中起重要作用。关于红豆蔻凝集素加CD28介导的信号传导和细胞因子分泌知之甚少。在本研究中,我们分析了用红豆蔻凝集素加抗CD28抗体交联CD28(CD28XL)刺激CD4 + T细胞后细胞内的信号转导事件。我们的结果表明,与单独用红豆蔻凝集素或单独用CD28XL刺激相比,Tec和T细胞活化连接蛋白的磷酸化增强。用红豆蔻凝集素或CD28XL刺激似乎不足以诱导白细胞介素(IL)-4分泌;然而,先用CD28XL刺激,再用红豆蔻凝集素刺激,可导致p38丝裂原活化蛋白激酶(MAPK)的磷酸化增强和IL-4分泌增加。然而,与用佛波酯12-肉豆蔻酸酯13-乙酸酯加离子霉素刺激相比,红豆蔻凝集素加CD28XL导致肿瘤坏死因子α分泌水平降低。添加p38抑制剂SB203580可抑制p38磷酸化和IL-4分泌。这些数据表明,单独的红豆蔻凝集素刺激似乎不足以促进Th2发育,而添加CD28共刺激可诱导Th2产生。我们提出,红豆蔻凝集素加CD28XL通过激活p38 MAPK诱导Th2分化。