Generation of CD4+ and CD8+ T lymphocyte responses by dendritic cells armed with PSA/anti-PSA (antigen/antibody) complexes
Generation of CD4+ and CD8+ T lymphocyte responses by dendritic cells armed with PSA/anti-PSA (antigen/antibody) complexes
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DOI：
10.1006/clim.2001.5115
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发表时间：
2001-12-01
影响因子：
8.6
通讯作者：
Mann, DL
中科院分区：
文献类型：
--
作者：
Berlyn, KA;Schultes, B;Mann, DL
树突状细胞（DC）获得抗原。包括受体在内的许多细胞表面结构。免疫球蛋白和甘露糖的Fe部分。关于通过这些受体摄取抗原对抗原加工和呈递的影响知之甚少。我们比较了DC在暴露于单独的前列腺特异性抗原（PSA）、靶向甘露糖受体的PSA（甘露糖基化PSA（PSA-m））或通过PSA与抗PSA抗体组合靶向Fe受体的PSA（AR 47.47）后产生CD 4（+）和CD 8（+）T细胞应答的能力。将自体CD 3（+）T细胞加入到单核细胞来源的未成熟DC中，所述DC已经用GM-CS/IL-4培养4天，暴露于抗原，并用CD 40 L或TNF α/IFN-α成熟。在几轮刺激后，通过使用细胞内IFN-γ产生来评估T细胞应答。怎么做细胞计数。在用暴露于PSA/抗PSA复合物的DC刺激后观察到CD 4（+）和CD 8（+）T细胞应答，而在用PSA武装的DC或PSA-m刺激后，CD 4（+）T细胞应答占主导地位。当用BLA等位基因限制性PSA肽脉冲的DC再攻击时，这些CD 8 + T细胞应答。这些结果表明，PSA和PSA-in主要通过有利于HLA II类呈递的途径进行加工，而PSA/抗PSA免疫复合物在单核细胞衍生的DC中通过I类和II类途径进行加工。这些发现在设计更有效的前列腺癌癌症疫苗方面具有潜在的应用价值。(C)2001年，爱思唯尔科学。
Dendritic cells (DC) acquire antigens. through a number of cell surface structures including receptors. for the Fe portion of immunoglobulins and mannose. Little is known about the effects of antigen uptake via these receptors on antigen processing and presentation. We compared the capacity of DC to generate CD4(+) and CD8(+) T cell responses after exposure to prostate-specific antigen (PSA) alone, PSA targeted to the mannose receptor (mannosylated PSA (PSA-m)), or PSA targeted to Fe receptors by combining PSA with an anti-PSA antibody (AR47.47). Autologous CD3(+) T cells were added to monocyte-derived immature DC that had been cultured with GM-CS/IL-4 for 4 days, exposed to antigen, and matured with CD40L or TNF alpha/ IFN-alpha. After several rounds of stimulation, T cell responses were assessed by intracellular IFN-gamma production using. How cytometry. Both CD4(+) and CD8(+) T cell responses were observed after stimulation with DC exposed to the PSA/anti-PSA complexes, whereas CD4(+) predominated over CD8(+) T cell responses after stimulation with PSA-armed DC or PSA-m. These CDS' T cells responded when rechallenged with DC pulsed with BLA allele-restricted PSA peptides. These results indicate that PSA and PSA-in are processed primarily through pathways that favor HLA Class II presentation, while the PSA/anti-PSA immune complexes are processed through both Class I and Class II pathways in monocyte-derived DC. These findings have potential applications in designing more effective cancer vaccines for prostate cancer. (C) 2001 Elsevier Science.