Department of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland.
PLoS One. 2012;7(3):e33276. doi: 10.1371/journal.pone.0033276. Epub 2012 Mar 12.
Alzheimer's disease (AD) is the most frequent form of dementia among elderly. Despite the vast amount of literature on non-specific immune mechanisms in AD there is still little information about the potential antigen-specific immune response in this pathology. It is known that early stages of AD include β-amyloid (Aβ)- reactive antibodies production and inflammatory response. Despite some evidence gathered proving cellular immune response background in AD pathology, the specific reactions of CD4(+) and CD8(+) cells remain unknown as the previous investigations yielded conflicting results. Here we investigated the CD4(+)CD28(+) population of human peripheral blood T cells and showed that soluble β-amyloids alone were unable to stimulate these cells to proliferate significantly, resulting only in minor, probably antigen-specific, proliferative response. On the other hand, the exposure of in vitro pre-stimulated lymphocytes to soluble Aβ peptides significantly enhanced the proliferative response of these cells which had also lead to increased levels of TNF, IL-10 and IL-6. We also proved that Aβ peptide-enhanced proliferative response of CD4(+)CD28(+) cells is autonomous and independent from disease status while being associated with the initial, ex vivo activation status of the CD4(+) cells. In conclusion, we suggest that the effect of Aβ peptides on the immune system of AD patients does not depend on the specific reactivity to Aβ epitope(s), but is rather a consequence of an unspecific modulation of the cell cycle dynamics and cytokine production by T cells, occurring simultaneously in a huge proportion of Aβ peptide-exposed T lymphocytes and affecting the immune system performance.
阿尔茨海默病（AD）是老年人中最常见的痴呆症形式。尽管有大量关于 AD 中非特异性免疫机制的文献，但关于这种病理学中潜在的抗原特异性免疫反应的信息仍然很少。已知 AD 的早期阶段包括β-淀粉样蛋白（Aβ）反应性抗体的产生和炎症反应。尽管有一些证据表明 AD 病理学中有细胞免疫反应背景，但 CD4(+)和 CD8(+)细胞的具体反应仍然未知，因为之前的研究结果相互矛盾。在这里，我们研究了人外周血 T 细胞中的 CD4(+)CD28(+)细胞群，并表明单独的可溶性β-淀粉样蛋白本身无法刺激这些细胞显著增殖，仅导致轻微的、可能是抗原特异性的增殖反应。另一方面，将体外预刺激的淋巴细胞暴露于可溶性 Aβ 肽显著增强了这些细胞的增殖反应，这也导致 TNF、IL-10 和 IL-6 水平升高。我们还证明，Aβ 肽增强的 CD4(+)CD28(+)细胞增殖反应是自主的，与疾病状态无关，而与 CD4(+)细胞的初始、体外激活状态相关。总之，我们认为 Aβ 肽对 AD 患者免疫系统的影响不依赖于对 Aβ 表位的特异性反应，而是 T 细胞细胞周期动力学和细胞因子产生的非特异性调节的结果，同时发生在大量暴露于 Aβ 肽的 T 淋巴细胞中，并影响免疫系统的性能。
