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1.
IL-7对早期胸腺细胞发育的作用   总被引:1,自引:0,他引:1  
胸腺基质细胞分泌白细胞介素7(IL-7)。IL-7是早期T细胞的重要生长因子之一。它能选择性促进CD4-CD8-和CD4+CD8-/CD4-CD8+细胞增殖。IL-7主要维持早期前体T细胞存活,同时保持其T前体细胞潜能。IL-7对胸腺细胞分化的作用目前仍有争议。  相似文献   

2.
胸腺基质细胞分泌白细胞介素7(IL-7)。IL-7是早期T细胞的重要生长因子之一。它能选择性促进CD4^-CD8^-和CD4^+CD8^-/CD4^-CD8^+细胞增殖。IL-7主要维持早期前体T细胞存活,同时保持其T前体细胞潜能。IL-7结胸腺细胞分化的作用目前仍有争议。  相似文献   

3.
蒋玖  童善庆 《微生物与感染》1995,18(5):16-17,38
本文简述近几年来丙型肝炎病毒(HCV)感染与宿主细胞免疫应答之间关系的研究进展,重点对HCV感染后体内CD4^+T细胞、CD8^+T细胞和细胞毒性T淋巴细胞(CTL)的免疫应答及其在免疫致病中的作用进行了讨论。  相似文献   

4.
以7690-Xu荧光染色法结合WuT3、WuT4、WuT8致敏红细胞花环实验观察经胸腺细胞分层液分离所得高密度亚群和低密度亚群人胎胸腺细胞的异质性荧光及其膜分化抗原CD3、CD4、CD8的表达。结果表明:不同胎龄胎儿胸腺细胞悬液呈现相似形态和相似分布特征的8种异质性荧光的细胞,其中,墨黑核细胞和桔红核细胞分布于两密度亚群,表型为CD3-CD4-CD8-;少数深蓝核和蓝核细胞分布于低密度亚群.表型为CD3+,属成熟的胸腺细胞;大多数深蓝核和蓝核细胞、灰蓝核细胞、灰黄核细胞及部分淡桔黄核细胞分布于高密度亚群,表型为CD3-、CD4+、CD8+,为处于中间发育阶段的胸腺细胞。推测这些细胞胞核由深蓝、蓝、灰蓝、灰黄到淡桔黄的荧光光谱的偏移可能与中间发育阶段所发生的生物及理化变化有关。  相似文献   

5.
将编码丙型肝炎病毒(HCV)E2蛋白417~750位氨基酸的DNA片段 克隆到真核表达载体pcDNA 3.1(-)中的CMV IE启动子下游,构建成HCV E2重组真核表达质粒 pcE2。ELISA法检测pcE2 DNA免疫兔血清中的E2抗体变化和维持规律,结果显示免疫20d已有 抗体产生,30d后开始进入高峰,40d时达到最高值,至第90d抗体水平保持平稳,抗体滴度 达到1∶1600左右。流式细胞计数仪(FACS)检测pcE2 DNA免疫鼠CD4+、CD8+T淋巴细胞变 化情况,与注射空载体pCDNA3.1(-)的阴性鼠相比,CD4+淋巴细胞水平略有上升,CD8+ 细胞水平有较大升高,增幅达35.46%。免疫组化检测结果显示注射pcE2的小鼠组织中有明显 的阳性着色,而注射pcDNA3.1(-)的对照组小鼠免疫组化结果为阴性。以上结果表明:pcE2 在实验动物内表达出的HCV E2蛋白可以引起免疫动物的体液免疫应答和细胞免疫应答,尤其 是MHC-1限制性杀伤性CD8+T淋巴细胞水平的提高对清除 病毒是十分有利的,因此HCV E2 DNA免疫有可能成为预防和治疗HCV感染的一条新途径。  相似文献   

6.
超抗原作为一类强大的免疫激活因子,可活化T细胞和抗原呈递细胞,其作用范围从T细胞增殖的诱导,众多细胞因子释放,免疫抑制到免疫耐受和免疫无反应性,并与自身免疫和免疫机能不全有关。超抗原由某些细胞,病毒,支原体和寄生虫产生,它可以激活比普抗原多达数千倍的T淋巴细胞(包括CD^+4和CD^+8T细胞),并可活化NK细胞和单核细胞。超抗原以不同于普通抗原的方式与抗原呈递细胞(APC)上MHCⅡ类子分子及T  相似文献   

7.
在应用双歧杆菌活菌制剂治疗慢乙肝期间,重点观察了T细胞亚群(CD3,CD4,CD8)、NK细胞(CD(16))、白细胞介素Ⅱ(IL-2)分泌细胞、肿瘤坏死因子(TNF)等细胞免疫指标治疗前后的动态变化,同时观察了病人血内毒素水平的动态变化和乙肝病毒标志物(HBVM)的改变。结果表明:(1)与对照组比较,双歧杆菌活菌制剂可使慢乙肝病人CD3+,CD4+数目明显增多,而对CD8+细胞数目无明显影响;(2)双歧杆菌活菌制剂可使CAH组的CD16+细胞显著增多(p<0.05);使CAH组和CPH组的IL-2分泌细胞均有非常显著和显著增加(分别p<0.01和p<0.05);(3)CAH组病人血中内毒素和TNF水平在双歧杆菌活菌制剂治疗后,匀出现非常显著降低(p<0.01);CPH组TNF水平较对照组无显著变化,但内毒素水平较对照组显著降低(p<0.05);(4)满疗程后(60天)CAH组有6例,CPH组有5例HBeAg阴转(分别为26.06%和25.0%),而对照组仅2例阴转(13.33%),两治疗组与对照组比较有显著性差异(p<0.05)。  相似文献   

8.
田兰  陈慰峰 《生命科学》1995,7(1):11-15
p56~(lck)与T细胞发育田兰,陈慰峰(北京医科大学免疫系100083)来源于骨髓的多能干细胞在胸腺内经过一系列复杂的发育过程成为功能成熟的T细胞。根据细胞表面CD4、CD8分子的表达,可将胸腺细胞分为4个不同的亚群,其发育顺序为CD4-CDS-...  相似文献   

9.
人免疫重建SCID小鼠的研究   总被引:2,自引:0,他引:2  
42只不渗漏SCID小鼠分别腹腔注射经冷冻、复苏的胎肝或胎肝加胎胸腺细胞,每鼠2×107活细胞,建立人胎肝细胞SCID小鼠模型Ⅰ和Ⅱ,研究人免疫系统。用人肝癌细胞(HHCC)免疫,SCID鼠出现初始免疫答应,血清人IgG平均滴度分别达到513.0±84.2ng/ml和719.7±201.6ng/ml,IgG峰值分别出现在免疫重建后10~12和10~14周,特异性抗HHCC抗体滴度分别达到1∶70.4±35.05和1∶294.4±168.52,免疫重建后7~8周龄,ABC法免疫组化染色,免疫鼠模型肝、脾中可检出标记人的CD3+、CD20+T和B淋巴细胞克隆和细胞岛。流式细胞仪检测了抗原免疫组和模型组外周血、脾脏、肝脏的人CD3+、CD4+、CD8+、CD19+、CD20+标记的淋巴细胞数,其中标记CD20+淋巴细胞平均值外周血3.12±3.03%、脾脏1.4±0.20%、肝脏2.32±1.49%。而无抗原免疫的模型组在肝脏仅有微量或检测不到人标记淋巴细胞。  相似文献   

10.
本文用多种T细胞和NK细胞单抗和免疫组织化学的ABC技术,在冰冻切片上对人扁桃体、淋巴结、牌和胸腺内T细胞亚群和NK细胞的分布进行了检测。结果显示,CD5、CD8、CD4、CD3和AIG3阳性细胞主要分布在扁桃体,淋巴结的副皮质区、脾的动脉周围淋巴鞘和胸腺,但各种抗体的反应强度不同。从各种T细胞工群的染色强度和形状看,胸腺髓质部的胸腺细胞相当于周围淋巴器官内的胸腺依赖区。胸腺内T细胞在分化过程中,质膜上的抗原也有相应变化。NK细胞主要分布在淋巴小结的生发中心,淋巴结和扁桃体的副皮质区,脾的红髓以及胸腺的筋质部。这些不同的分布,说明NK细胞不仅与淋巴小结的活动有关,可能还参与机体的免疫调节功能。  相似文献   

11.
To define early stages of T cell maturation during human fetal thymic development, we have used mAb reactive with CD2, CD3, and TCR molecules in indirect immunofluorescence assays on a series of early human fetal thymic specimens. Using a technique of quantitating the relative proportions of fluorescent-positive cells present in tissue sections, we found at 8.5 wk of gestational age after arrival of CD7+ T cell precursors into the thymic rudiment, 60% of thymic CD7+ cells were CD2+, 4% were CD3+ and none was TCR-delta+ or TCR beta+. Moreover, cells reactive with anti-CD2 antibodies against T11(2) and T11(3) epitopes of CD2 as well as thymic stromal cells expressing the CD2 ligand, lymphocyte function associated Ag-3, were also present at 8.5 wk. From 9.5 wk to birth TCR beta+ cells increased to include greater than 90% of all CD7+ cells while TCR-delta+ cells fell from a peak of 11% of CD7+ cells at 9.5 wk to 1% of CD7+ cells at birth. These data suggest that epitopes of CD2 molecules are expressed early on during fetal thymic development. Moreover, these data suggest that CD7+, CD2+, cytoplasmic CD3+ T cell precursors in man give rise to both TCR-delta+ T cells as well as to T cells expressing TCR-alpha beta.  相似文献   

12.
In pre-Talpha (pTalpha) gene-deleted mice, the positively selectable CD4+ CD8+ double-positive thymocyte pool is only 1% that in wild-type mice. Consequently, their peripheral T cell compartment is severely lymphopenic with a concomitant increase in proportion of CD25+ FoxP3+ regulatory T cells. Using mixed bone marrow chimeras, where thymic output was 1% normal, the pTalpha(-/-) peripheral T cell phenotype could be reproduced with normal cells. In the pTalpha(-/-) thymus and peripheral lymphoid organs, FoxP3+ CD4+ cells were enriched. Parabiosis experiments showed that many pTalpha(-/-) CD4+ single-positive thymocytes represented recirculating peripheral T cells. Therefore, the enrichment of FoxP3+ CD4+ single-positive thymocytes was not solely due to increased thymic production. Thus, the pTalpha(-/-) mouse serves as a model system with which to study the consequences of chronic decreased thymic T cell production on the physiology of the peripheral T cell compartment.  相似文献   

13.
Expression and function of the UM4D4 antigen in human thymus   总被引:3,自引:0,他引:3  
UM4D4 is a newly identified T cell surface molecule, distinct from the Ag receptor and CD2, which is expressed on 25% of peripheral blood T cells, resting or activated. Monoclonal anti-UM4D4 is mitogenic for T cells and T cell clones. Since alternative activation pathways independent of Ag/MHC recognition may be important in thymic differentiation, the expression and function of UM4D4 was examined in human thymus. UM4D4 was found on the surface of 6% of thymocytes. All thymocyte subsets contained UM4D4+ cells but expression was greatest on thymocytes that were CD1- (12%), CD3+ (11%) and especially CD4-CD8- (18%). CD3+CD4- CD8- cells, most of which bear the gamma delta-receptor, were greater than or equal to 50% + for UM4D4. Moreover, anti-UM4D4 was comitogenic for thymocytes together with PMA or IL-2. Anti-UM4D4 also reacted strongly with a subset of thymic epithelial cells in both cortex and medulla. Dual color fluorescence microscopy, with anti-UM4D4 and antibodies to other thymic epithelial Ag, showed UM4D4 expression on neuroendocrine thymic epithelium but not on thymic fibrous stroma. Thus, UM4D4 is expressed on, and represents an activation pathway for, a subset of thymic T cells. In addition, this determinant, initially identified as a novel T cell activating molecule, is broadly expressed by neuroendocrine thymic epithelium. Although the function of UM4D4 on the thymic epithelial cells is not yet clear, it is possible that UM4D4 represents a pathway for the functional activation of a subset of the thymic epithelium as well as a subset of thymocytes, thus playing a dual role in T cell differentiation.  相似文献   

14.
Using an intrathymic injection assay on B10 Thy-1 congenic mice, it was demonstrated that thymic prelymphoma cells first developed within the thymuses from 4 to 8 days after split-dose irradiation and were detected in more than 63% of the test donor thymuses when examined at 21 and 31 days after irradiation. Moreover, some mice (25%) at 2 mo after split-dose irradiation had already developed thymic lymphomas in their thymuses. To characterize these thymic prelymphoma cells, the thymocytes from B10 Thy-1.1 mice 1 mo after irradiation were stained with anti-CD4 and anti-CD8 mAb and were sorted into four subpopulations. These fractionated cells were injected into the recipient thymuses to examine which subpopulation contained thymic prelymphoma cells. The results indicated that thymic prelymphoma cells existed mainly in CD4- CD8- and CD4- CD8+ thymocyte subpopulations and also in CD4+ CD8+ subpopulation. T cell lymphomas derived from CD4- CD8- prelymphoma cells had mainly CD4- CD8- or CD4- CD8+ phenotypes. T cell lymphomas developed from CD4- CD8+ prelymphoma cells mainly expressed CD4- CD8+ or CD4+ CD8+ phenotype. T cell lymphomas originating from CD4+ CD8+ prelymphoma cells were mainly CD4+ CD8+ but some CD4- CD8+ or CD4+ CD8- cells were also present. These thymic prelymphoma cells were further characterized phenotypically in relation to their expression of the marker defined by the mAb against J11d marker and TL-2 (thymus-leukemia) Ag, which is not expressed on normal thymocytes of B10.Thy-1.2 or B10.Thy-1.1 strain, but appears on the thymocytes of lymphomagenic irradiated mice. The results indicated that the prelymphoma cells existed in J11d+, TL-2+ cells.  相似文献   

15.
Lymphocyte activation gene-3 (LAG-3; CD223) is structurally similar to CD4 and binds to MHC class II with a 100-fold higher affinity than that of CD4. Soluble LAG-3 (sLAG-3Ig) might be useful for immunotherapy by inducing MHC class II-mediated cell activation. A new form of sLAG-3Ig was constructed containing a critical binding site (D1 and D2 region) to MHC class II, combined with a Fc portion of an immunoglobulin gamma1. After treatment of sLAG-3Ig in fetal thymic organ culture from DO11.10 transgenic mouse, CD4(+) T cell precursors were increased in the positive selection but not affected in the negative selection. Further analysis by treating sLAG-3Ig on thymic epithelial cells revealed that CD40 and MHC class II were up-regulated. These results may demonstrate that the treatment of sLAG-3Ig increases the precursor frequency of CD4(+) T cells by activation of thymic epithelial cells.  相似文献   

16.
17.
Thymic shared Ag-2 (TSA-2) is a 28-kDa, glycophosphatidylinitosol-linked cell surface molecule expressed on various T cell and thymic stromal cell subsets. It is expressed on most CD3-CD4-CD8-, CD4+CD8+, and CD3highCD4-CD8+ thymocytes but is down-regulated on approximately 40% of CD3highCD4+CD8- thymocytes. Expression on peripheral TCR-alphabeta+ T cells is similar to that of CD3+ thymocytes, although a transient down-regulation occurs with cell activation. Consistent with the recent hypothesis that emigration from the thymus is an active process, recent thymic emigrants are primarily TSA-2-/low. TSA-2 expression reveals heterogeneity among subpopulations of CD3highCD4+CD8- thymocytes and TCR-gamma delta+ T cell previously regarded as homogenous. The functional importance of TSA-2 was illustrated by the severe block in T cell differentiation caused by adding purified anti-TSA-2 mAb to reconstituted fetal thymic organ culture. While each CD25/CD44-defined triple-negative subset was present, differentiation beyond the TN stage was essentially absent, and cell numbers of all subsets were significantly below those of control cultures. Cross-linking TSA-2 on thymocytes caused a significant Ca2+ influx but no increase in apoptosis, unless anti-TSA-2 was used in conjunction with suboptimal anti-CD3 mAb. Similar treatment of mature TSA-2+ T cells had no effect on cell survival or proliferation. This study reveals TSA-2 to be a functionally important molecule in T cell development and a novel indicator of heterogeneity among a variety of developing and mature T cell populations.  相似文献   

18.
In nonobese diabetic (NOD) mice, T cells play a major role in mediating autoimmunity against pancreatic islet beta-cells. We and others previously reported that age-related alterations in the thymic and peripheral T cell repertoire and function occur in prediabetic NOD mice. To study the mechanism responsible for these T cell alterations, we examined whether a defect exists in the thymus of NOD mice at the level of TCR-mediated signaling after activation by Con A and anti-CD3. We found that thymocytes from NOD mice respond weakly to Con A- and anti-CD3-induced proliferation, compared with thymocytes from control BALB/c, BALB.B, (BALB.B x BALB.K)F1, C57BL/6, and nonobese non-diabetic mice. This defect correlates with the onset of insulitis, because it can be detected at 7 to 8 weeks of age, whereas younger mice displayed a normal T cell responsiveness. Thymic T cells from (NOD x BALB/c)F1 mice, which are insulitis- and diabetes-free, exhibit an intermediate stage of unresponsiveness. This T cell defect is not due to a difference in the level of CD3 and IL-2R expression by NOD and BALB/c thymocytes, and both NOD CD4+ CD8- and CD4- CD8+ mature thymic T cells respond poorly to Con A. BALB/c but not NOD thymic T cells respond to Con A in the presence of either BALB/c or NOD thymic APC, suggesting that the thymic T cell defect in NOD mice is intrinsic to NOD thymic T cells and is not due to an inability of NOD APC to provide a costimulatory signal. The defect can be partially reversed by the addition of rIL-2 to NOD thymocytes. To determine whether a defect in signal transduction mediates this NOD thymic T cell unresponsiveness, we tested whether these cells elevate their intracellular free Ca2+ ion concentration in response to Con A. An equivalent Con A-induced increase in Ca2+ ion concentration in both NOD and BALB/c thymocytes was observed, suggesting a normal coupling between the CD3 complex and phospholipase C in NOD thymocytes. In contrast to their low proliferative response to Con A or anti-CD3, NOD thymocytes respond normally (i.e., as do BALB/c thymocytes) to the combinations of PMA plus the Ca2+ ionophore ionomycin and PMA plus Con A but weakly to Con A plus ionomycin. Our data suggest that the age-related NOD thymocyte unresponsiveness to Con A and anti-CD3 results from a defect in the signaling pathway of T cell activation that occurs upstream of protein kinase C activation.  相似文献   

19.
CD4 repopulation can be achieved in T cell-depleted, thymectomized mice grafted with xenogeneic porcine thymus tissue. These CD4 T cells are specifically tolerant of the xenogeneic porcine thymus donor and the recipient, but are positively selected only by porcine MHC. Recent studies suggest that optimal peripheral survival of naive CD4 T cells requires the presence of the same class II MHC in the periphery as that of the thymus in which they were selected. These observations would suggest that T cells selected on porcine thymic MHC would die rapidly in the periphery, where porcine MHC is absent. Persistent CD4 reconstitution achieved in mice grafted with fetal porcine thymus might be due to increased thymic output to compensate for rapid death of T cells in the periphery. Comparison of CD4 T cell decay after removal of porcine or murine thymic grafts ruled out this possibility. No measurable role for peripheral murine class II MHC in maintaining the naive CD4 pool originating in thymic grafts was demonstrable. However, mouse class II MHC supported the conversion to, survival, and/or proliferation of memory-type CD4 cells selected in fetal porcine thymus. Thus, the same MHC as that mediating positive selection in the thymus is not critical for maintenance of the memory CD4 cell pool in the periphery. Our results support the interpretation that xenogeneic thymic transplantation is a feasible strategy to reconstitute CD4 T cells and render recipients tolerant of a xenogeneic donor.  相似文献   

20.
IL-2 contributes to the production, function, and homeostasis of CD4+CD25+ T(reg) cells. However, it remains uncertain whether IL-2 is essential for the development of T(reg) cells in the thymus, their homeostasis in the periphery, or both. The present study was undertaken to investigate the contribution of IL-2 during thymic T(reg) cell development and its maintenance in peripheral immune tissue. Relying on genetic mouse models where IL-2R signaling was either completely blocked or selectively inhibited in peripheral CD4+CD25+ T(reg) cells, we show that the IL-2/IL-2R interaction is active in the thymus at the earliest stage of the development of T(reg) cells to promote their expansion and to up-regulate Foxp3 and CD25 to normal levels. Furthermore, CD4+CD25+Foxp3+ T(reg) cells with impaired IL-2-induced signaling persist in the periphery and control autoimmunity without constant thymic output. These peripheral T(reg) cells with poor responsiveness to IL-2 exhibited slower growth and extended survival in vivo, somewhat lower suppressive activity, and poor IL-2-dependent survival in vitro. Mixed thymic and bone marrow chimeric mice showed that wild-type-derived T(reg) cells were substantially more effective in populating peripheral immune tissue than T(reg) cells with impaired IL-2 signaling. Collectively, these data support the notion that normally IL-2 is a dominant mechanism controlling the number of thymic and peripheral T(reg) cells.  相似文献   

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