Mbawuike I N, Acuna C, Caballero D, Pham-Nguyen K, Gilbert B, Petribon P, Harmon M
Acute Viral Respiratory Disease Unit, Influenza Research Center, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
Cell Immunol. 1996 Oct 10;173(1):64-78. doi: 10.1006/cimm.1996.0252.
Old and young Balb/c mice, 24--26 and 2--4 months old, respectively, were infected with a 0.1 LD50 of influenza A/Taiwan/1/86 (A/H1N1) virus by small particle aerosol. Lung virus titers were determined 4, 6, 8, 12, and 17 days later. Old mice had significantly higher virus titers than young mice (P < 0.05-0.0001) and shed virus up to Day 17, while young mice were free of virus by Day 12. Splenic MHC class I CD8+ CTL activity (P < 0.08--0.001) and IFN-gamma production (0.1-0.008) measured on Days 8, 12, and 17 were significantly lower among old mice than among young mice. Coadministration of liposomal influenza vaccine with monophosphoryl lipid A (MPL) resulted in enhanced CD8+ CTL response and IFN-gamma production among old mice (35 and 12,000 times, respectively). These results demonstrate that MPL stimulates CTL and Th1 cytokines (IFN-gamma) in aged mice and may serve to reverse age-related CD8+ CTL deficiency and reduce severe influenza disease in elderly human populations.
分别为24 - 26月龄和2 - 4月龄的老年和幼年Balb/c小鼠，通过小颗粒气溶胶感染0.1半数致死剂量（LD50）的甲型流感病毒/台湾/1/86（A/H1N1）。在4、6、8、12和17天后测定肺病毒滴度。老年小鼠的病毒滴度显著高于幼年小鼠（P < 0.05 - 0.0001），并且在第17天仍有病毒排出，而幼年小鼠在第12天时已无病毒。在第8、12和17天测量的老年小鼠脾脏MHC I类CD8 + 细胞毒性T淋巴细胞（CTL）活性（P < 0.08 - 0.001）和γ干扰素产生量（0.1 - 0.008）显著低于幼年小鼠。脂质体流感疫苗与单磷酰脂质A（MPL）共同给药导致老年小鼠的CD8 + CTL反应和γ干扰素产生增强（分别提高35倍和12,000倍）。这些结果表明，MPL可刺激老年小鼠的CTL和Th1细胞因子（γ干扰素），可能有助于逆转与年龄相关的CD8 + CTL缺陷，并减少老年人群中的严重流感疾病。
