Mosenson Jeffrey A, McNulty John A
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Stritch School of Medicine, Maywood, IL 60153, USA.
BMC Immunol. 2006 Jan 11;7:1. doi: 10.1186/1471-2172-7-1.
Homeostatic trafficking of lymphocytes in the brain has important relevance to the understanding of CNS disease processes. The pineal gland of the chicken contains large accumulations of lymphocytes that suggest an important role related to homeostatic circadian neuro-immune interactions. The purpose of this initial study was to characterize the lymphocyte subsets in the pineal gland and quantitate the distribution and frequency of lymphocyte phenotypes at two time points over the 24-hour light:dark cycle.
PALT comprised approximately 10% of the total pineal area. Image analysis of immunocytochemically stained sections showed that the majority of lymphocytes were CD3+ (80%) with the remaining 20% comprising B-cells and monocytes (Bu-1+), which tended to distribute along the periphery of the PALT. T-cell subsets in PALT included CD4+ (75-80%), CD8+ (20-25%), TCRalphabeta/Vbeta1+ (60%), and TCRgammadelta+ (15%). All of the T-cell phenotypes were commonly found within the interfollicular septa and follicles of the pineal gland. However, the ratios of CD8+/CD4+ and TCRgammadelta+/TCRalphabeta/Vbeta1+ within the pineal tissue were each 1:1, in contrast to the PALT where the ratios of CD8+/CD4+ and TCRgammadelta+/TCRalphabeta/Vbeta1+ each approximated 1:4. Bu-1+ cells were only rarely seen in the pineal interstitial spaces, but ramified Bu-1+ microglia/macrophages were common in the pineal follicles. Effects of the 24-h light:dark cycle on these lymphocyte-pineal interactions were suggested by an increase in the area of PALT, a decline in the density of TCRalphabeta/Vbeta1+ cells, and a decline in the area density of Bu-1+ microglia at the light:dark interphase (1900 h) compared to the dark:light interphase (0700 h).
The degree of lymphocyte infiltration in the pineal suggests novel mechanisms of neuro-immune interactions in this part of the brain. Our results further suggest that these interactions have a temporal component related to the 24-hour light:dark cycle and that CD8+ and TCRgammadelta+ T-cells are preferentially recruited to the pineal follicles. Pineal microglia/macrophages were common and represent an important candidate for mediating these lymphocyte-pineal interactions via secretion of cytokines and chemokines.
淋巴细胞在脑内的稳态运输对于理解中枢神经系统疾病过程具有重要意义。鸡的松果体含有大量淋巴细胞聚集,这表明其在稳态昼夜神经免疫相互作用中发挥重要作用。这项初步研究的目的是鉴定松果体中的淋巴细胞亚群,并在24小时明/暗周期的两个时间点定量淋巴细胞表型的分布和频率。
松果体相关淋巴组织(PALT)约占松果体总面积的10%。对免疫细胞化学染色切片的图像分析显示,大多数淋巴细胞为CD3+(80%),其余20%为B细胞和单核细胞(Bu-1+),它们倾向于沿PALT的周边分布。PALT中的T细胞亚群包括CD4+(75 - 80%)、CD8+(20 - 25%)、TCRαβ/Vβ1+(60%)和TCRγδ+(15%)。所有T细胞表型常见于松果体的滤泡间隔和滤泡内。然而,松果体组织中CD8+/CD4+和TCRγδ+/TCRαβ/Vβ1+的比例均为1:1,而在PALT中,CD8+/CD4+和TCRγδ+/TCRαβ/Vβ1+的比例均约为1:4。Bu-1+细胞在松果体间隙中很少见,但分支状的Bu-1+小胶质细胞/巨噬细胞在松果体滤泡中很常见。与暗/明相间期(0700 h)相比,在明/暗相间期(1900 h),PALT面积增加、TCRαβ/Vβ1+细胞密度下降以及Bu-1+小胶质细胞的面积密度下降,提示了24小时明/暗周期对这些淋巴细胞 - 松果体相互作用的影响。
松果体中淋巴细胞浸润的程度提示了该脑区神经免疫相互作用的新机制。我们的结果进一步表明,这些相互作用具有与24小时明/暗周期相关的时间成分,并且CD8+和TCRγδ+ T细胞优先被募集到松果体滤泡。松果体小胶质细胞/巨噬细胞很常见,是通过分泌细胞因子和趋化因子介导这些淋巴细胞 - 松果体相互作用的重要候选者。