Cohen-Sfady Michal, Nussbaum Gabriel, Pevsner-Fischer Meirav, Mor Felix, Carmi Pnina, Zanin-Zhorov Alexandra, Lider Ofer, Cohen Irun R
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
J Immunol. 2005 Sep 15;175(6):3594-602. doi: 10.4049/jimmunol.175.6.3594.
We recently reported that soluble 60-kDa heat shock protein (HSP60) can directly activate T cells via TLR2 signaling to enhance their Th2 response. In this study we investigated whether HSP60 might also activate B cells by an innate signaling pathway. We found that human HSP60 (but not the Escherichia coli GroEL or the Mycobacterial HSP65 molecules) induced naive mouse B cells to proliferate and to secrete IL-10 and IL-6. In addition, the HSP60-treated B cells up-regulated their expression of MHC class II and accessory molecules CD69, CD40, and B7-2. We tested the functional ability of HSP60-treated B cells to activate an allogeneic T cell response and found enhanced secretion of both IL-10 and IFN-gamma by the responding T cells. The effects of HSP60 were found to be largely dependent on TLR4 and MyD88 signaling; B cells from TLR4-mutant mice or from MyD88 knockout mice showed decreased responses to HSP60. Care was taken to rule out contamination of the HSP60 with LPS as a causative factor. These findings add B cells to the complex web of interactions by which HSP60 can regulate immune responses.
我们最近报道，可溶性60-kDa热休克蛋白（HSP60）可通过TLR2信号直接激活T细胞，增强其Th2反应。在本研究中，我们调查了HSP60是否也可能通过先天信号通路激活B细胞。我们发现，人HSP60（而非大肠杆菌GroEL或分枝杆菌HSP65分子）可诱导幼稚小鼠B细胞增殖并分泌IL-10和IL-6。此外，经HSP60处理的B细胞上调了其MHC II类分子及共刺激分子CD69、CD40和B7-2的表达。我们测试了经HSP60处理的B细胞激活同种异体T细胞反应的功能能力，发现反应性T细胞分泌的IL-10和IFN-γ均增加。发现HSP60的作用很大程度上依赖于TLR4和MyD88信号；来自TLR4突变小鼠或MyD88基因敲除小鼠的B细胞对HSP60的反应降低。已注意排除HSP60被LPS污染作为致病因素。这些发现表明，HSP60可通过复杂的相互作用网络调节免疫反应，B细胞也参与其中。
