Differential activation of cell-mediated immune functions by encapsulated and surface-linked liposomal antigens.
Differential activation of cell-mediated immune functions by encapsulated and surface-linked liposomal antigens.
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通过封装和表面连接的脂质体抗原差异激活细胞介导的免疫功能。
作者：
André Fortin;E. Shahum;Krzysztof Krzystyniak;H. Thérien
如果脂质体与蛋白质抗原物理结合，则脂质体可作为强效佐剂。然而，它们对免疫反应的影响因这种连接的性质而异，表面连接和封装的抗原具有不同的性质。细胞分析和细胞因子测量表明，这种差异可能是由于T淋巴细胞群的不同激活。表面连接抗原似乎优先刺激CD4+ T细胞增殖并成熟为典型的Th1表型；这可以通过致敏脾细胞CD4+/CD8+比值的正变化、干扰素- γ的大量产生和白细胞介素-4分泌的缺失来证明。相反，包被抗原在刺激脾细胞增殖的同时，对CD4+/CD8+比值没有显著影响，并且在没有白细胞介素-4分泌的情况下，仅诱导低水平的干扰素- γ产生。这些结果表明，CD4+和CD8+群体在包封抗原的反应中都扩增，但不诱导典型的Th1或Th2表型。高分辨率免疫细胞化学研究表明，T细胞群的这种差异激活可能与抗原进入专业抗原呈递细胞的不同细胞内运输有关。表面连接抗原主要停留在内体室中，在那里它可能与主要组织相容性（MHC） II类产物相关联，以呈递给CD4+ T细胞，而被包裹的抗原逃逸到细胞质中，到达MHC I类途径，呈递给CD8+ T细胞。因此，结果表明，这两种脂质体抗原刺激细胞介导的免疫，尽管不同。这种行为差异可能在设计佐剂以优先增强特定细胞毒性效应功能方面具有实际意义。
Liposomes act as powerful adjuvants if physically associated with a protein antigen. Their effect on the immune response, however, varies with the nature of this linkage, surface-linked and encapsulated antigens having different properties. Cytometric analysis and cytokine measurements indicate that this difference may be due to the differential activation of T lymphocyte populations. Surface-linked antigen appears to preferentially stimulate CD4+ T cells to proliferate and mature into a typical Th1 phenotype; this is indicated by a positive shift in the CD4+/CD8+ ratio of sensitized splenocytes, a massive production of interferon-gamma, and the absence of interleukin-4 secretion. In contrast, encapsulated antigen, while stimulating spleen cell proliferation, does not significantly affect the CD4+/CD8+ ratio and induces only low levels of interferon-gamma production in the absence of interleukin-4 secretion. These results suggest that CD4+ and CD8+ populations are both expanded in response to encapsulated antigen but that neither typical Th1 nor Th2 phenotypes are induced. High-resolution immunocytochemical investigations show that this differential activation of T cell populations may be related to a different intracellular trafficking of antigens into professional antigen-presenting cells. Whereas surface-linked antigen remains predominantly in endosomal compartments where it may be associated with major histocompatibility (MHC) class II products for presentation to CD4+ T cells, encapsulated antigen escapes into the cytosol, reaching the MHC class I pathway for presentation to CD8+ T cells. The results therefore suggest that both liposomal antigens stimulate cell-mediated immunity albeit differently. This behavioral difference may be of practical importance in the design of adjuvants for the preferential potentiation of specific cytotoxic effector functions.