Ke Y, McGraw C L, Hunter R L, Kapp J A
Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Cell Immunol. 1997 Mar 15;176(2):113-21. doi: 10.1006/cimm.1997.1084.
Nonionic triblock copolymers are relatively nontoxic adjuvants that induce high-titer, long-lasting antibody responses. We have previously shown that these adjuvants also induce cell-mediated immunity including lymphokine production by CD4(+) T cells and cytolytic responses by CD8(+) T cells. These copolymers are thought to modulate hydrophobic adhesive interactions between antigens (Ag) and lymphoid cells. We sought to test the hypothesis that copolymers facilitate uptake of exogenous Ag by antigen-presenting cells (APC) using an in vitro model system. Our data show that nonionic triblock copolymers enhanced presentation of soluble ovalbumin (OVA) to the major histocompatibility complex (MHC) class II-restricted CD4(+) T cells and MHC class I-restricted CD8(+) T cells, respectively. Presentation of OVA via the class I pathway was enhanced by copolymers in both phagocytic and nonphagocytic APC. However, copolymers did not enhance binding of peptides to the MHC molecules on APC, presentation of endogenously synthesized Ag, or presentation of exogenous Ag delivered by electroporation. These results provide additional evidence that these nonionic triblock copolymers can serve as powerful adjuvants for augmenting both humoral and cell-mediated immunity to protein Ag.
非离子三嵌段共聚物是相对无毒的佐剂，可诱导产生高滴度、持久的抗体反应。我们之前已经表明，这些佐剂还能诱导细胞介导的免疫反应，包括CD4(+) T细胞产生淋巴因子以及CD8(+) T细胞产生细胞溶解反应。这些共聚物被认为可调节抗原（Ag）与淋巴细胞之间的疏水粘附相互作用。我们试图使用体外模型系统来检验共聚物促进抗原呈递细胞（APC）摄取外源性Ag这一假说。我们的数据表明，非离子三嵌段共聚物分别增强了可溶性卵清蛋白（OVA）向主要组织相容性复合体（MHC）II类限制性CD4(+) T细胞和MHC I类限制性CD8(+) T细胞的呈递。在吞噬性和非吞噬性APC中，共聚物均增强了OVA通过I类途径的呈递。然而，共聚物并未增强肽与APC上MHC分子的结合、内源性合成Ag的呈递或电穿孔递送的外源性Ag的呈递。这些结果提供了额外的证据，表明这些非离子三嵌段共聚物可作为强大的佐剂，增强针对蛋白质Ag的体液免疫和细胞介导免疫。
