鲤主要免疫器官CD4L、CD8α和CD8β表达细胞的分布特征

自1975 年在硬骨鱼类中发现T 细胞存在的证据1以来, 单克隆抗体技术、免疫组化和原位杂交等技术的应用, 使鱼类T 细胞及其亚群和功能的研究成为可能。从20 世纪80 年代起, 人们开始尝试通过各种方法例如用胸腺细胞、多聚甲醛固定的胸腺细胞(DLT15)、胸腺细胞膜(WCL9)、肠白细胞膜(WCL38)免疫小鼠进而制备抗鱼类T细胞的单克隆抗体。       

Contrasted TCRβ Diversity of CD8+ and CD8? T Cells in Rainbow Trout

Teleost fish express highly diverse naive TCRβ (TRB) repertoires and mount strong public and private clonal responses upon infection with pathogens. Fish T cells express typical markers such as CD8, CD4-1 and CD4-2, CD3, CD28 and CTLA4. Fish CD8⁺ T cells have been shown to be responsible for antigen-specific cell-mediated cytotoxicity in in vitro systems using histo-compatible effector and target cells. We compare here the complexity of TRB repertoires between FACS sorted CD8⁺ and CD8⁻ T cells from spleen and pronephros of rainbow trout. In contrast to human, while the TRB repertoire is highly diverse and polyclonal in CD8⁺ T cells of naïve fish, it appeared very different in CD8⁻ lymphocytes with irregular CDR3 length distributions suggesting a dominance of activated clones already in naïve fish or the presence of non conventional T cells. After infection with a systemic virus, CD8⁺ T cells mount a typical response with significant skewing of CDR3 length profiles. The infection also induces significant modifications of the TRB repertoire expressed by the CD8⁻ fraction, but for a different set of V/J combinations. In this fraction, the antiviral response results in an increase of the peak diversity of spectratypes. This unusual observation reflects the presence of a number of T cell expansions that rise the relative importance of minor peaks of the highly skewed distributions observed in unchallenged animals. These results suggest that the diversity of TRB expressed by CD8⁺ and CD8⁻ αβ T cells may be subjected to different regulatory patterns in fish and in mammals.     

CD4~+T、CD8~+T、CD4~+/CD8~+与慢性乙肝不同中医体质存在相关性

探讨外周血CD4~+、CD8~+T水平与慢性乙型肝炎不同中医体质的关系。选取2016年2月至2017年3月在我院治疗的慢性乙型感染患者143例,其中平和质35例、气虚质40例、阴虚质21例、湿热质20例,气郁质16例、其他11例,采用流式细胞仪检测外周血T淋巴细胞亚群。不同中医体质患者性别、年龄、病程及HBV-DNA含量比较差异无统计学意义(p0.05);平和质患者AST为342.21(142.42,513.46)U/L,明显低于其他患者(p0.05);气虚质患者AST为512.40(322.81,726.50)U/L,明显高于其他患者(p0.05);气郁质及其他体质患者ALT分别为381.64(210.41,501.72)U/L和370.43(200.41,470.63)U/L,明显高于平和质、气虚质、阴虚质和湿热质患者(p0.05);平和质和气虚质患者外周血CD4~+T细胞分别为(39.10±2.01)%和(39.10±2.01)%,明显低于阴虚质、湿热质、气郁质及其他体质患者(p0.05);气郁质及其他体质患者CD8~+T细胞分别为(25.43±1.33)%和(25.24±1.31)%,明显低于平和质、气虚质、阴虚质和湿热质患者(p0.05);阴虚质、气郁质及其他体质患者分别为(1.71±0.09)、(1.75±0.08)和(1.78±0.09),明显高于平和质、气虚质和湿热质患者(p0.05)。慢性乙肝不同中医体质与CD4~+T、CD8~+T和以及肝功能有密切关系。关键词     

紫外线照射下小鼠T细胞CD4和CD8的表达

紫外线对机体健康的影响主要有物理性损伤 ,如引起皮肤表面的红肿 ,疼痛 ,出现水泡 ,产生皱褶 ,并出现色素沉着 ,皮肤老化等现象。严重者由于紫外线对机体的光毒性作用 ,皮肤内的各种色素集团在吸收光线的同时产生大量的氧自由基 ,进而造成ＤＮＡ分子的损伤 ,引起基因突变、癌化 ,直至细胞死亡。近年来有研究报道 ,通过紫外线照射 ,抑制机体的细胞免疫机能 ,降低接触性迟发型超敏反应 ,甚至由于抑制Ｔ细胞而出现对特异性半抗原无免疫反应状态 ,但同时也使机体对细菌、寄生虫等的侵袭易感。为进一步探讨紫外线照射对机体免疫防御机能的影响 ,…     

Identification of CD3ε, CD4, CD8β splice variants of Atlantic salmon

In vertebrates, CD3 complex and CD4 and CD8 co-receptors are essential for signal transduction during T cell activation. In the present study, we report the mRNA spliced variants of the Atlantic salmon CD3ε, CD4 and CD8β and the effect of pathogen encounter on the expression of these variants. CD3ε is alternatively spliced in thymus, head kidney, spleen and gills to give rise to the complete mRNA sequence and to an alternative product that lacks the transmembrane exon. CD4 is also alternatively spliced in the thymus, head kidney, spleen and gills to form two variants, although the alternative product is barely detectable. The alternative product lacks the exon 1B encoding the D1 domain, which is essential for binding to MHC class II proteins. Two amplicons were also found for the CD8β gene; sequencing analysis revealed that the main PCR product corresponds to the previously reported CD8β sequence, whereas the variant sequence encodes a potential protein that lacks the Ig-like domain. The expression of CD3, CD4, CD8β genes also analyzed in head kidney of LPS-treated and IPNV infected salmon and different patterns of expression were observed. The presence and balance of the different variants of T cell co-receptors could be related to the ability of fish to induce a particular type of immune response, as well as, the ability of the pathogen to modify the fish immune response.     

肿瘤患者CD8+T细胞中CD28表达的研究进展

CD28与B7结合形成的共刺激信号是T细胞激活的第二信号,肿瘤患者CD8^＋T细胞上CD28分子在肿瘤免疫中发挥着重要作用。人体抗肿瘤免疫主要由CD8^＋T细胞介导,根据CD28的表达与否可将CD8^＋T细胞分为细胞毒T细胞（CD8^＋CD28^＋,CTL）和抑制性T细胞（CD8^＋C28^-,Ts）。CTL是体内杀伤肿瘤细胞的主要功能性细胞之一,当该细胞与肿瘤接触时,通过共刺激信号而被激活,发挥其对肿瘤细胞的杀伤作用;Ts在机体的免疫耐受中发挥作用。现就肿瘤患者CD8^＋T细胞上CD28的表达作一综述。     

Selective support of a mouse thymus epithelial cell line （MTEC1） to the viability and proliferation of CD4＋CD8—,CD4^—CD8^—,and CD4^＋CD8^＋thymocytes in vitro

The MTEC1 cell line,established in our laboratory,is a normal epithelial cell line derived from thymus medulla of Balb/c mice and these cells constituteively produce multiple cytokines.The selection of thymic microenvironment on developing T cells was investigated in an in vitro system.Unseparated fresh thymocytes from Balb/c mice were cocultured with MTEC1 cells or/and MTEC1-SN,then,the viability,proliferation and phenotypes of cultured thymocytes were assessed.Without any exogenous stimulus,both MTEC1 cells and MTEC1-SN were able to maintain the viability of thymocytes,while only the MTEC1 cells,not the MTEC1-SN,could directly activate thymocytes to exhibit moderate proliferation,indicating that the proliferative signal is delivered through cell surface interatcions of MTEC1 cells and thymocytes.Phenotype analysis on FACS of viable thymocytes after coculture revealed that MTEC1 cells preferentially activate the subsets of CD4^ CD8^-,CD4^ CD^8 and CD^4- CD^8- thymocytes;whereas MTEC1-SN preferentially maintained the viability of CD4^ CD^8- and CD4^-CD8^ thymocyte subsets.For the Con A-activated thymocytes.both MTEC1 cells and MTEC1-SN provided accessory signal(s) to significantly increase the number of viable cells and to markedly enhance the proliferation of thymocytes with virtually equal potency,phenotyped as CD4^ CD8^-,CD4^-CD8^ ,and CD^4-CD8^-subests,In summary,MTEC1 cells displayed Selection of thymic epithelial cells on thymocyte subsets. selective support to the different thymocyte subsets,and the selectivity is dependent on the status of thymocytes.     

Identification of Cytolytic CD161?CD56+ Regulatory CD8 T Cells in Human Peripheral Blood

We previously developed methods for establishing CD8 regulatory T cell (Treg) clones from normal human peripheral blood and demonstrated that these clones were capable of killing T cell receptor (TCR)-activated autologous CD4 T cells. Based on phenotypic and functional characterization of the CD8 Treg clones, we have identified a corresponding population of endogenous CD8 Treg in normal human peripheral blood. These cells appear morphologically as large lymphocytes with abundant cytoplasm and have the following unique phenotype: CD3⁺CD8⁺CD161⁻CD56⁺. The majority of CD8 Treg express CD45RA and CD62L with low or negative expression of CD45RO, CD25, CD27, CD28 and CCR7. The expression of CD94 and NKG2a on CD8 Treg was elevated compared to conventional CD8 T cells. Following in vitro activation, this T cell subset is capable of killing TCR-activated CD4 T cells. These studies identify an endogenous CD8 Treg population in humans and it will now be possible to characterize these cells in a variety of clinical conditions.     

抗CD3mAb诱导TN细胞向过渡型CD8单阳性细胞分化

本实验观察了在IL-7维持TN细胞生长的体外细胞培养系统中,抗CD 3 mAb对TN细胞分化的作用。发现抗CD 3 mAb在体外能诱导TN细胞分化产生CD 4~-CD 8~ 及部分CD 4~(lo)CD 8~ 细胞。由于多数CD 8~ 细胞为TCRβ~-,故抗CD 3 mAb诱导产生的CD 4~-CD 8~ 细胞是DN向DP分化的不成熟过渡状态细胞。抗TCR βmAb也能诱导CD 4~-CD 8~ 细胞产生,但其诱导分化能力弱于抗CD3 mAb。在体外细胞培养条件下,抗CD 3mAb诱导的DN→DP转化伴有IL-2 Rα表达下调,并且IL-7诱导的TCRβ分子表达也受到抑制。当TN细胞在IL-7条件下培养3天后,抗CD 3 mAb便失去诱导TN细胞分化的能力,表明抗CD 3 mAb诱导的TN细胞分化可能是通过细胞表面pre-TCR复合体进行的。     

记忆性CD8细胞产生、维持及CD4细胞的辅助作用

记忆性T淋巴细胞的形成及其在体内的长期维持,是一个复杂的多层次调控过程,CD4细胞及相关的细胞因子通过间接和直接作用,对CD8记忆细胞的形成起到重要的促进作用。CD8记忆细胞需要不同信号的刺激以保证其在体内的长期维持,是一个动态平衡的过程。