Double-Negative T Cell Levels Correlate with Chronic Graft-versus-Host Disease Severity

Chronic graft-versus-host disease (cGVHD) is a major complication, affecting 50% to 80% of long-term survivors of allogeneic hematopoietic stem cell transplantation. Current cGVHD therapies are neither specific nor curative, and patients are typically maintained for several months to years under immunosuppressive regimens that are associated with important side effects and increased susceptibility to life-threatening infections. As a result, continued investigation into the pathology of the disease and the search for novel diagnostic and therapeutic strategies to treat cGVHD remains a high priority. We report that the cellular dynamics of various immune cell subsets are related to cGVHD onset and severity in a cohort of allogeneic hematopoietic stem cell transplantation recipients. We document a decrease in the proportion of CD45RO⁺ CD4^?CD8^? (double-negative [DN]) T cells at the onset of cGVHD, a time at which serum levels of B cell activating factor and B cells are increased. We also find that DN T cell levels are correlated with cGVHD severity. Our present findings are in line with the view that activated DN T cells exhibit their immunoregulatory potential by eliminating B cells in vivo. Taken together, these findings suggest that maintaining elevated DN T cell numbers before the onset of cGVHD may prevent pathological B cell responses.     

H-2~b和H-2~d单体型小鼠MHCI类分子结合的HFRSV蛋白抗原表位的预测

本文通过对Ｈ－２ｂ和Ｈ－２ｄ单体型小鼠主要组织相容性抗原Ｉ类分子结合抗原肽的分析，建立了一个计算机预测模型，并对肾综合征出血热病毒核蛋白（ＮＰ）及囊膜糖蛋白Ｇ１和Ｇ２可与Ｂａｌｂ／ｃ小鼠（Ｈ－２ｄ）和Ｃ５７ＢＬ／６（Ｈ－２ｂ）小鼠ＭＨＣＩ类分子相结合的抗原表位进行了分析，预测出可分别与Ｈ－２Ｋｂ，Ｈ－２Ｄｂ，Ｈ－２Ｋｄ，Ｈ－２Ｄｄ和Ｈ－２Ｌｄ结合的核蛋白表位，依此各有７，１４，４，０和８个；囊膜糖蛋白Ｇ１＋Ｇ２的表位，依次有１４，１９，２７，２和４４个。     

T cell differentiation and generation of the antigen-specific T cell repertoire in man: observations in MHC class II deficiency

The circulating T cell pool of an MHC class II-deficient patient was shown to lack the MHC class II-specific T cell functions. This was demonstrated by the absence of MHC class Il-specific alloreactive T cells and a substantially decreased number of circulating CD4⁺ lymphocytes. The patient's T cells did respond to an allostimulus, although the restriction pattern of this reaction remains speculative. The function and distribution of peripheral T cell subsets from the patient resemble findings in MHC class II-deficient mice, which also lack interaction of T cell precursors with MHC class Il-bearing accessory cells during thymic differentiation. Our data support the concept that Tcell differentiation in humans is similar, and that the human MHC-restricted Tcell repertoire depends on prior interaction of T cell precursors with self MHC.     

白细胞介素2与调节性T细胞介导的免疫耐受

调节性T细胞(Tregs)可以诱导机体对自身抗原和过敏原产生免疫耐受,从而维持机体免疫稳态.白细胞介素(IL)-2是一种具有双向免疫调节作用的糖蛋白,其不仅可以增强免疫反应,更重要的是可以维持Tregs的稳定及其介导的免疫耐受.研究IL-2与Tregs功能活性及其介导的免疫耐受的关系对更好地了解免疫相关性疾病的发病机制和指导临床正确使用IL-2或IL-2拮抗剂具有重要意义.     

An animated landscape representation of CD4+ T‐cell differentiation,variability, and plasticity: Insights into the behavior of populations versus cells

Recent advances in understanding CD4⁺ T‐cell differentiation suggest that previous models of a few distinct, stable effector phenotypes were too simplistic. Although several well‐characterized phenotypes are still recognized, some states display plasticity, and intermediate phenotypes exist. As a framework for reexamining these concepts, we use Waddington's landscape paradigm, augmented with explicit consideration of stochastic variations. Our animation program “LAVA” visualizes T‐cell differentiation as cells moving across a landscape of hills and valleys, leading to attractor basins representing stable or semistable differentiation states. The model illustrates several principles, including: (i) cell populations may behave more predictably than individual cells; (ii) analogous to reticulate evolution, differentiation may proceed through a network of interconnected states, rather than a single well‐defined pathway; (iii) relatively minor changes in the barriers between attractor basins can change the stability or plasticity of a population; (iv) intrapopulation variability of gene expression may be an important regulator of differentiation, rather than inconsequential noise; (v) the behavior of some populations may be defined mainly by the behavior of outlier cells. While not a quantitative representation of actual differentiation, our model is intended to provoke discussion of T‐cell differentiation pathways, particularly highlighting a probabilistic view of transitions between states.     

条件性血管瘤转基因小鼠模型的建立

目的：采用条件性转基因策略构建小鼠血管瘤动物模型,并对其表型进行鉴定。方法：构建血管内皮细胞特异性表达启动子Tie2驱动的鼠多瘤病毒中间T基因（ PyMT）表达质粒（ pTie2?PyMT）,采用DNA显微注射方法,将血管内皮特异性表达的PyMT目的基因导入供体C57BL／6J小鼠的雄原核中,再移植到假孕鼠的输卵管中,产生转基因首建鼠。 PCR方法检测目的基因整合情况,检查转基因鼠基因型,观察转基因鼠表型,对于转基因鼠出现的新生物进行组织学及免疫组织化学检测。采用GraphPad Prism 5．0软件包对实验数据进行统计学分析。结果：经测序分析证实,pTie2?PyMT质粒中PyMT、Tie2启动子和Tie2增强子序列等组成元件被正确克隆、连接,且阅读框正确。出生小鼠基因型经PCR鉴定证实,阳性的转基因小鼠均出现血管瘤样新生物表型。血管瘤样新生物主要表达部位在小鼠的耳、舌、皮肤、黏膜、肝等部位,组织学检查证实为血管瘤样病变,免疫组织化学方法证实新生物的内皮细胞表达PyMT蛋白及血管内皮标志物CD31。结论：Tie2启动子驱动下的PyMT基因可以在小鼠体内诱发血管瘤,该模型鼠可用于血管瘤发病机制的研究。条件控制下的转基因技术是一种有效的建立血管瘤动物模型的方法。     

Potential function of TGF-β isoforms in maturation-stage ameloblasts

Objectives

To investigate potential functions of transforming growth factor-beta (TGF-β) isoforms in maturation-stage ameloblasts during amelogenesis.

手术分娩对产妇和新生儿血中T淋巴细胞的影响

目的 探讨手术分娩对产妇和新生儿T淋巴细胞亚群数量的影响.方法 足月分娩产妇60例,依据分娩方式及手术时机分为自然分娩(NL)组、择期剖宫产(PCS)组、急诊剖宫产(ECS)组各20例;分别采集分娩时的产妇外周血和新生儿脐血,应用流式细胞仪检测T细胞各亚群的百分比.结果 NL组、PCS组、ECS组产妇血中T淋巴细胞亚群CD3+(69.15±13.24)%、(73.50±4.86)%、(68.68±7.50)%;CD3+CD4+(32.03±9.44)%、(36.35±11.82)%、(34.88±7.54)%;CD3+CD8+(29.83±6.01)%、(30.59±7.30)%、(28.08±4.09)%;CD4+/CD8+1.09±0.37、1.33±0.65、1.25±0.27各组间差异均无统计学意义(P＞0.05);新生儿脐血:PCS组中由于CD4+的减少而呈现CD4+/CD8+的比值明显低于NL、ECS组,分别为2.71±0.86、3.52±1.50、3.30±1.03(P＜0.05).结论 产妇血中T淋巴细胞亚群数量不受手术分娩以及产程影响;PCS可能会加剧新生儿对某些病原体的易感性.