CD4+ T cells determine the ability of spleen cells from F1 hybrid mice to induce neonatal tolerance to alloantigens and autoimmunity in parental mice

Spleen cells from F₁ hybrid mice injected into newborn parental mice induce a state of cytolytic unresponsiveness to the corresponding alloantigens. However, these mice develop a transient autoimmune syndrome characterized by the production of multiple autoantibodies and glomerulonephritis. Previous reports indicated that the depletion of F₁ donor T cells, shortly prior the injection into parental mice, does not interfere with any of these events. Here, we have explored whether the continuous absence of T cells in F₁ mice influences the ability of their spleen cells to induce neonatal tolerance to alloantigens and the associated autoimmune manifestations. Our results revealed that spleen cells from athymic (BALB/c × C57BL/6) F₁ hybrid (CB6F₁) nulnu mice or from euthymic CB6F₁ mice depleted from birth of CD4⁺ T cells, but not of CD8⁺ T cells, are unable to induce neonatal tolerance to alloantigens and autoimmune manifestations. By contrast, the partial reconstitution of T cells in CB6F¹ nulnu mice, after the neonatal graft of a syngeneic thymus, restored the capacity of spleen cells from these mice to induce tolerance and autoimmunity when injected into newborn BALB/c mice. These results demonstrate that the functional defect of spleen cells from athymic CB6F₁ nulnu mice to induce neonatal tolerance to alloantigens is directly related to the long-term absence of mature CD4⁺ T cells. Interestingly, a new increase in the titers of anti-DNA Ab was observed when spleen cells from athymic CB6F₁ nulnu mice were injected into adult BALB/c mice that had been tolerized at birth with normal CB6F₁ spleen cells. This finding indicates that B cells from CB6F₁ nulnu mice recover their capacity to interact with alloreactive Th2 cells when they are placed into mice having functional CD4⁺ T cells. These data indicate that the continuous absence of CD4⁺ T cells causes a reversible functional defect in F₁ spleen cells that determines their inability to induce neonatal tolerance and autoimmunity.     

柳州地区女性新生儿高胆红素血症患儿G6PD基因突变类型及临床特点--附七例报告

目的探讨柳州地区籍女性新生儿黄疸儿G6PD基因突变类型与其临床表现特点之间的关系.方法采用基因芯片技术检测了7例柳州地区籍女性新生儿黄疸儿的G6PD基因突变类型,并对其临床表现特点进行分析.结果 (1)7例女患儿G6PD基因突变共检出4种类型,包括G1388A、A95G、G1376T及G392T,其中5例为杂合子.(2)G6PD酶学检查5例表现为中间型,且临床黄疸症状较轻,治疗效果好.结论柳州地区籍女性新生儿黄疸儿的G6PD基因突变类型多见G1388A、A95G、G1376T突变,以杂合子改变占多数.     

The advantage of mucosal immunization for polysaccharide-specific memory responses in early life

The aim of vaccination is to rapidly elicit protective immunity and generate memory for sustained protection. We studied the induction and persistence of polysaccharide (PS)-specific memory in neonatal and infant mice primed with pneumococcal conjugate (Pnc1-TT) by assessing the response to native pneumococcal PS (PPS-1), the kinetics of the PPS-1-specific IgG response to a second Pnc1-TT dose and affinity maturation. A subcutaneous (s.c.) Pnc1-TT booster induced a rapid increase in PPS-1-specific IgG, indicating efficient priming for memory by a single dose of Pnc1-TT already at 1 week of age. High levels were maintained for >12 weeks. However, a PPS-1 booster induced no response in neonatal or infant mice. The adjuvant LT-K63 significantly enhanced the IgG response and affinity to Pnc1-TT by both the s.c. and the intranasal (i.n.) route in all age groups. In neonatal and infant mice, PPS-1 and LT-K63 induced a booster response only when given i.n. following either s.c. or i.n. priming with Pnc1-TT and LT-K63. In contrast, PPS-1 with or without LT-K63 administered s.c. compromised the ongoing PPS-1-specific response elicited in neonatal mice by either s.c. or i.n. priming with Pnc1-TT and LT-K63. These results demonstrate the advantage of the mucosal route for elicitation of PS-specific memory responses in early life.     

Superfluousness of motor innervation for the formation of muscle spindles in neonatal rats

Summary Muscle spindles form de novo in reinnervated muscles of neonatal rats treated with nerve growth factor. Whether the spindles can also form in muscle reinnervated only by afferents was investigated by removing the lumbosacral segment of the spinal cord immediately after crushing the nerve to the medial gastrocnemius muscle at birth, and administering nerve growth factor for 10 days afterwards. As predicted, the medial gastrocnemius muscles were reinnervated by afferents, but not efferents. No motor endplates were visible on any muscle fibers, and extrafusal fibers were atrophied. The reinnervated muscles contained spindle-like encapsulations of one to four fibers at 5, 7, 9 and 30 days after the nerve crush. The number of spindles as well as encapsulated fibers exceeded that of normal medial gastrocnemius muscles. The encapsulated fibers resembled typical intrafusal fibers. They had normal sensory-muscle contacts, but no motor endings. The fibers displayed equatorial clusters of myonuclei and expressed the spindle-specific slow-tonic myosin heavy chain isoform at postnatal day 30. Thus, efferents are not essential for the formation and differentiation of muscle spindles in reinnervated muscles of neonatal rats.     

Characterization of host CD4+ T lymphocytes in mice neonatally tolerized to alloantigens

BALB/c mice injected at birth with semi-allogeneic F1 spleen cells become tolerant to alloantigens as shown by their CTL unresponsiveness to the corresponding alloantigen and the persistence of donor F1 cells into the BALB/c host. Moreover, these mice develop a transient systemic lupus erythematosis-like autoimmune syndrome characterized by splenomegaly, glomerulonephritis, thrombocytopenia and abnormal serological findings, such as several autoantibodies and IgG1 hypergammaglobulinemia. Recent studies done in our laboratory have shown that donor F1 B cells persisting in the host are responsible for the production of autoantibodies and must be activated in vivo by the host CD4⁺ T lymphocytes in a MHC class II-restricted fashion. In the present work, we have focused our attention on the ability of splenic CD4⁺ T cells recovered at different periods from BALB/c mice injected at birth with (CBA/Ca × BALB. Igh^b) Fl spleen cells to interact with and activate F1 semi-allogeneic spleen cells in vitro. We show that (i) only CD4⁺ T cells from 2- and 3-week-old tolerant BALB/c mice preferentially produce IL-4 and IL-5 in response to a F1 semi-allogeneic in vitro stimulation, (ii) CD4⁺ T cells purified from 3-week-old tolerant BALB/c mice are able to induce in vitro IgG and IgM production by F1 B cells. Taken together, these results strongly suggest that host CD4+ T cells, belonging to the TH2 subset progressively lose their reactivity towards the F1 semi-allogeneic persistent B cells, reaching a state of unresponsiveness that correlates with the disappearance of serum autoantibodies and autoimmune pathology.     

Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis

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核转录因子-κB在缺氧预处理抑制心肌细胞凋亡中的作用

目的 :研究缺氧预处理 (hypoxicpreconditioning ,HPC)对于心肌细胞蛋白激酶C(PKC)和核转录因子κB (NF κB)表达的影响 ,及其在缺氧复氧诱导心肌细胞凋亡中的作用。方法 :在培养的SD乳鼠心肌细胞制作缺氧 /复氧 (H/R)模型 ,以荧光素染料Hoechst3 3 2 5 8测定心肌细胞凋亡率 ;制备心肌细胞蛋白提取物 ,以新PKCε亚型 (nPKCε)特异性抗体测定nPKCε相对蛋白含量 ;以抗NF κB抗体检测NF κB的表达 ;并以PKC抑制剂H7与心肌细胞预孵育后 ,观察H7对于HPC诱导的PKC和NF κB表达上调以及心肌细胞保护作用的影响。结果 :缺氧复氧造成心肌细胞凋亡 ,HPC可以降低心肌细胞H/R后凋亡率 ,并诱导nPKCε和NF κB表达上调 ;PKC抑制剂H7可以消除HPC诱导的PKC、NF κB表达上调和心肌细胞保护作用。结论 :HPC可以提高乳鼠心肌细胞对于H/R的耐受性 ,其机制涉及PKC介导的NF κB表达上调。     

6024例分娩的方式选择与新生儿结局

目的探讨阴道分娩和剖宫产对新生儿的风险。方法对6024例妊娠的分娩方式、剖宫产指征以及新生儿结局回顾性分析。结果剖宫产率为35.3%,其指征主要是头盆不称、社会因素、宫内窘迫、臀位等。分娩新生儿6016例,其中因各种疾患转儿科822例,占13.5%。主要转科原因为早产儿低体重、窒息、高胆红素血症和吸入综合症,各疾病发病率与分娩方式无关。结论剖宫产没有增加新生儿的风险,仍是解决难产的重要手段,但应严格控制手术指征。     

高压氧对新生大鼠缺氧缺血性脑损伤后在体神经干细胞的影响

目的： 新生鼠的神经生发区-室管膜下区（SVZ） 和海马齿状回（DG）聚集了多种不同发育阶段神经干细胞（NSCs），它们可分化产生新的神经元和胶质细胞。本研究探讨缺氧缺血性脑损伤（HIBD）对脑生发区NSCs的损伤及高压氧（HBO）对此损伤的影响。从在体NSCs 探讨HBO对新生大鼠HIBD的保护作用机制。 方法： 新生7 d龄SD大鼠随机分为4组：① 正常对照组（CON，n=16）；② HIBD 模型组（HIBD，n=16）；③ 高压空气组（HBA，n=16）；④HBO治疗组（n=16）。Rice法复制HIBD模型，并予HBA或HBO治疗，每天1次共7 d。BrdU免疫组化显示在体NSCs。并取损伤侧脑SVZ区组织，体外NSCs培养并进行神经干细胞球计数。 结果： HIBD组生发区在体BrdU 阳性细胞和体外培养的神经干细胞球数目明显少于对照组。HBO组SVZ区的BrdU阳性细胞增多；体外培养的神经干细胞球增多。HBA组增加不明显。 结论： 新生大鼠HIBD后生发区NSCs减少，HBO治疗可以减轻HIBD后NSCs的死亡。HBA治疗无明显作用。     

Aberrant retinal projections to midbrain targets mediate spared visual orienting function in hamsters with neonatal lesions of superior colliculus

Summary Rodents, cats, and most nonmammalian vertebrates with bilateral tectal deafferentation or ablation in adulthood are extremely deficient at orienting to visual stimuli; yet animals with neonatal lesions of superficial layers of the superior colliculus (SC) show partial sparing of this response, particularly for targets in the central visual field. In this study, we sought to determine whether these spared orienting abilities are mediated by aberrant retinal projections to the remaining intermediate layers of the SC, or whether visual cortex (VC) mechanisms or alternative behavioral strategies are responsible. Neonatal golden hamsters received either bilateral heat lesions of the SC (rlSC), or a heat lesion of the right SC and enucleation of the right eye (rSCrE). This latter procedure causes axons from the left eye to recross the tectal midline and terminate in the wrong (left) SC (Schneider 1973). As adults, both groups of hamsters were extremely deficient in visually guided approach to stationary targets, although rlSC-lesioned hamsters showed some sparing for central field targets and rSCrE-lesioned hamsters often made wrong-direction turns for targets in the left peripheral field. We then subjected both groups of neonatally lesioned hamsters to bilateral aspiration lesions of the VC. Retesting showed no change in visual orienting behavior as a result of the cortical lesions. Labeling of the optic tract with horseradish peroxidase (HRP) revealed abundant aberrant retinal projections to remaining intermediate layers of the SC and thalamic nucleus lateralis posterior (LP), as well as supernormal innervation of pretectal nuclei, the dorsal terminal nucleus of the accessory optic tract, and the ventral nucleus of the lateral geniculate body (LGv). We conclude that the spared visual orienting capabilities of hamsters with rlSC and rSCrE lesions are mediated by the aberrant midbrain projections, and that cortical mechanisms are not involved in spared visual orienting functions following these neonatal lesions.