Mechanisms of enhanced antigen-specific T cell response following vaccination with a novel peptide-based cancer vaccine and systemic interleukin-2 (IL-2).
Mechanisms of enhanced antigen-specific T cell response following vaccination with a novel peptide-based cancer vaccine and systemic interleukin-2 (IL-2).
复制标题
接种新型肽癌症疫苗和全身性白细胞介素 2 (IL-2) 后增强抗原特异性 T 细胞反应的机制。
DOI：
10.1016/s0264-410x(03)00096-3
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发表时间：
2003
期刊：
影响因子：
5.5
通讯作者：
Gillanders,WilliamE
中科院分区：
文献类型：
--
作者：
Nguyen,ChristopheL;Salem,MohamedL;Rubinstein,MarkP;Demcheva,Marina;Vournakis,JohnN;Cole,DavidJ;Gillanders,WilliamE
全身白介素-2 （IL-2）治疗已被证明可提高基于肽的癌症疫苗的临床疗效。然而，涉及这种复杂反应的机制仍然不明确。众所周知，IL-2是一种有效的T细胞生长因子，但最近的研究表明，IL-2还通过增加增殖T细胞对凋亡的易感性参与T细胞免疫反应的调节。使用过继转移模型，我们证明了在基于肽的疫苗接种后，系统IL-2的管理显著增强了初级和记忆免疫反应。为了明确IL-2治疗对抗原特异性T细胞反应的作用机制，我们探索了T细胞增殖、凋亡和转运的动力学。全身IL-2治疗似乎并没有在接种疫苗后立即改变T细胞增殖动力学，但确实延长了增殖反应。此外，IL-2治疗没有显著影响增殖T细胞的凋亡。然而，这种治疗确实增强了l-选择素（CD62L）对活化抗原特异性T细胞的下调，并改变了它们的运输，证实了它们潜在的治疗价值。我们的研究结果支持在基于肽的疫苗接种后使用全身IL-2，并表明IL-2治疗通过延长增殖反应和改变抗原特异性T细胞的运输来增强初级和记忆免疫反应。
Systemic interleukin-2 (IL-2) therapy has been shown to enhance the clinical efficacy of peptide-based cancer vaccines. However, the mechanisms involved in this complex response remain poorly defined. IL-2 is known to be a potent T cell growth factor, but recent studies suggest that IL-2 is also involved in the regulation of T cell immune responses by increasing the susceptibility of proliferating T cells to apoptosis. Using an adoptive transfer model, we demonstrate that the administration of systemic IL-2 significantly enhances the primary and memory immune responses following peptide-based vaccination. In order to define the mechanisms of IL-2 therapy on the antigen-specific T cell response, the kinetics of T cell proliferation, apoptosis, and trafficking were explored. Systemic IL-2 therapy did not appear to alter the kinetics of T cell proliferation immediately following vaccination, but did prolong the proliferative response. Furthermore, IL-2 therapy did not significantly influence apoptosis of proliferating T cells. Such therapy did, however, potentiate l-selectin (CD62L) downregulation on activated antigen-specific T cells, and altered their trafficking confirming their potential therapeutic value. Our findings support the use of systemic IL-2 following peptide-based vaccination, and suggest that IL-2 therapy enhances the primary and memory immune responses by prolonging the proliferative response and altering the trafficking of antigen-specific T cells.