Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with β-amyloid
Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with β-amyloid
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DOI：
10.1093/intimm/dxg049
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发表时间：
2003-04-01
影响因子：
4.4
通讯作者：
Agadjanyan, MG
中科院分区：
文献类型：
--
作者：
Cribbs, DH;Ghochikyan, A;Agadjanyan, MG
在野生型小鼠中检查佐剂对针对A β免疫疗法（A β（42）肽）的T（h）1和T（h）2免疫应答的作用。用Abeta（42）序列的重叠寡聚体进行的精细表位分析鉴定了1 - 15区为显性B细胞表位。6 - 20肽仅被来自施用在完全弗氏佐剂（CFA）、明矾或TiterMax Gold（TMG）中配制的Abeta（42）肽的小鼠的抗血清微弱地识别。然而，用与QS 21混合的Abeta（42）免疫的小鼠诱导了对6 - 20肽的显著抗体应答。发现的唯一T细胞表位在Abeta的6 - 28序列内（42）。QS 21和CFA诱导的体液反应最强，明矾居中，TMG最弱。对Abeta特异性抗体同种型的分析表明，明矾主要诱导T（h）2型免疫应答，而TMG、CFA和QS 21将免疫应答转向T（h）1表型。用Abeta（40）肽刺激来自Abeta免疫小鼠的脾细胞诱导显著不同的细胞因子表达谱。QS 21和CFA诱导显著的IFN-γ、IL-4和肿瘤坏死因子-α表达，而明矾主要诱导IL-4产生。由于T（h）1型免疫应答与许多自身免疫性疾病有关，而T（h）2型免疫应答已被证明可抑制自身免疫性疾病，因此佐剂的选择对于设计安全有效的阿尔茨海默病免疫疗法可能至关重要。
The role of adjuvant on the T(h)1 and T(h)2 immune responses to Abeta-immunotherapy (Abeta(42) peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Abeta(42) sequence identified the 1-15 region as a dominant B cell epitope. The 6-20 peptide was recognized only weakly by antisera from mice administrated with Abeta(42) peptide formulated in complete Freund's adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Abeta(42) mixed with QS21 induced a significant antibody response to the 6-20 peptide. The only T cell epitope found was within the 6-28 sequence of Abeta(42). QS21 and CFA induced the strongest humoral response to Abeta, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Abeta indicates that alum induces primarily T(h)2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a T(h)1 phenotype. Stimulation of splenocytes from Abeta-immunized mice with Abeta(40) peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-gamma, IL-4 and tumor necrosis factor-alpha expression, whereas alum induced primarily IL-4 production. As T(h)1-type immune responses have been implicated in many autoimmune disorders, whereas T(h)2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer's disease.