Goodman M G, Weigle W O
J Immunol. 1985 Jun;134(6):3808-11.
The relative capacities of two classes of immunomodulator to augment the deficient immunity of senescent mice were evaluated. Bacterial lipopolysaccharide (LPS) was used as the prototype for modulators that depend on normal membrane function for signal transduction, and 8-mercaptoguanosine (8MGuo) represents a class of immunomodulator that transverses the cell membrane and induces its effects from an intracellular location. The current studies demonstrate that 8MGuo induces polyclonal immunoglobulin production in cultures from both young and senescent mice, whereas LPS can induce such activity only in cell cultures from young adult mice. Furthermore, LPS was unable to enhance the magnitude of antigen-specific responses in aged mice, in contrast to the marked adjuvant effects of 8MGuo. 8MGuo, but not LPS, provided an effective T cell-like signal that induced responsiveness to a T-dependent antigen in B cells from senescent mice. These B cells thus were able to transduce antigen-specific (first) but not nonspecific (second) signals, provided by agents such as LPS, across the cell membrane. Together, these observations suggest that the C8-derivatized guanine ribonucleosides substantially improve the immunodeficiency of aging by short-circuiting a B cell defect and providing a perceived second signal to lymphocytes from senescent animals.
评估了两类免疫调节剂增强衰老小鼠免疫缺陷的相对能力。细菌脂多糖（LPS）被用作依赖正常膜功能进行信号转导的调节剂的原型，而8-巯基鸟苷（8MGuo）代表一类穿过细胞膜并从细胞内位置诱导其效应的免疫调节剂。目前的研究表明，8MGuo可在年轻和衰老小鼠的培养物中诱导多克隆免疫球蛋白产生，而LPS仅能在年轻成年小鼠的细胞培养物中诱导这种活性。此外，与8MGuo的显著佐剂效应相反，LPS无法增强老年小鼠抗原特异性反应的强度。8MGuo而非LPS提供了一种有效的T细胞样信号，诱导衰老小鼠B细胞对T依赖性抗原产生反应。因此，这些B细胞能够跨细胞膜转导由LPS等试剂提供的抗原特异性（第一）而非非特异性（第二）信号。总之，这些观察结果表明，C8衍生的鸟嘌呤核糖核苷通过绕过B细胞缺陷并为衰老动物的淋巴细胞提供可感知的第二信号，显著改善了衰老引起的免疫缺陷。
