Petitto J M, Gariepy J L, Gendreau P L, Rodriguiz R, Lewis M H, Lysle D T
Brain Institute, University of Florida, Gainesville, Florida, 32610-0256, USA.
Brain Behav Immun. 1999 Jun;13(2):175-86. doi: 10.1006/brbi.1998.0539.
In previous studies, we found differences in cellular immune responsiveness in Institute for Cancer Research (ICR) mice selectively bred for high and low levels of aggression. Compared to the high aggressive line, the low aggressive line had low levels of natural killer (NK) and T cell activity and increased susceptibility to tumor development. To dissect further this novel association, experiments were designed to test two competing hypotheses. The first hypothesis was that the phenotypic expression of the line differences in NK cell activity are dependent on and regulated by the expression of high and low levels aggressive behavior in the lines. The alternative hypothesis was that the differences in immune status are independent of the expression of aggression by the lines, suggesting linkage between a subset of genes involved in determining these complex behavioral and immunological traits or pleiotropic gene effects on both traits. In Experiment 1, three conditions of postweaning social experience (mice singly housed, group housed within line, or group housed between lines) were tested in males to determine whether experiential conditions which modify the expression of aggression would in turn modify the line differences in NK cell activity. This experiment revealed that the difference in NK cell activity between high aggressive and low aggressive male mice was attributable to line only. The different postweaning social conditions examined had no effect on modifying the differences in NK activity, and social dominance hierarchy did not correlate with levels of NK cell activity. Whereas males of the high and low lines exhibit differences in aggressive behaviors across most contexts, females do not exhibit such differences except in response to an intruder during the postpartum period. Therefore, in Experiment 2 we compared the NK cell activity of nulliparous females of the high and low aggressive lines. Under these conditions, females of the low aggressive line had low levels of NK activity compared to high aggressive females (differences comparable to those seen between males of the high and low lines). Taken together, these experiments lend support to the hypothesis that this association may be due to a genetic linkage between subsets of genes involved in determining these complex behavioral and immunological traits, or may possibly represent a fortuitous association which occurred during the selective breeding.
在之前的研究中，我们发现，在为高攻击性和低攻击性水平而选择性培育的癌症研究所（ICR）小鼠中，细胞免疫反应存在差异。与高攻击性品系相比，低攻击性品系的自然杀伤（NK）细胞和T细胞活性水平较低，且对肿瘤发生的易感性增加。为了进一步剖析这种新的关联，我们设计了实验来检验两种相互竞争的假设。第一个假设是，NK细胞活性品系差异的表型表达取决于品系中高、低水平攻击性行为的表达，并受其调节。另一个假设是，免疫状态的差异与品系攻击性行为的表达无关，这表明在决定这些复杂行为和免疫特征的基因子集中存在连锁关系，或者存在对这两种特征都有影响的多效基因效应。在实验1中，对雄性小鼠测试了三种断奶后社会经历条件（单独饲养、同品系群体饲养或不同品系群体饲养），以确定改变攻击性行为表达的经验条件是否会反过来改变NK细胞活性的品系差异。该实验表明，高攻击性和低攻击性雄性小鼠之间的NK细胞活性差异仅归因于品系。所研究的不同断奶后社会条件对改变NK活性差异没有影响，且社会优势等级与NK细胞活性水平无关。虽然高、低品系的雄性在大多数情况下攻击性行为存在差异，但雌性除了在产后对入侵者有反应外，不表现出这种差异。因此，在实验2中，我们比较了高攻击性和低攻击性品系未生育雌性的NK细胞活性。在这些条件下，与高攻击性雌性相比，低攻击性品系的雌性NK活性水平较低（差异与高、低品系雄性之间的差异相当）。综上所述，这些实验支持了这样一种假设，即这种关联可能是由于参与决定这些复杂行为和免疫特征的基因子集之间存在遗传连锁，或者可能代表了在选择性育种过程中发生的一种偶然关联。
