舌下含服粉尘螨滴剂脱敏治疗对特应性皮炎患者中辅助性T细胞作用的研究

目的 探讨舌下含服粉尘螨滴剂脱敏治疗对特应性皮炎(atopic dermatitis,AD)患者辅助性T细胞(T helper cells,Th)的作用.方法 用酶联免疫吸附测定(enzyme-linked immuno sorbent assay,ELISA)方法检测AD患者舌下含服粉尘螨滴剂组(sublingual immunotherapy,SLIT组)和对照组治疗前后的外周血Th1(IFN-γ)、Th2(IL-4)、Th17(IL-17)的水平,用流式细胞技术检测两组治疗前后的调节性T细胞(regulatoryT cells,Treg)数量.然后用两独立样本t或校正t(t')检验对两组患者治疗前和治疗后的组内以及治疗后组间的IFN-γ、IL-4、IL-17和Treg水平分别进行对比研究.结果 SLIT组治疗后IL-4、IL-17较治疗前明显下降,IFN-γ和Treg较治疗前明显升高,差异有统计学意义(P＜0.05).且SLIT组治疗后较对照组治疗后IL-4、IL-17下降更明显,IFN-γ升高更明显,差异有统计学意义(P＜0.05).SLIT组治疗后Treg细胞数量较对照组治疗后升高更多,但差异无统计学意义(P＞0.05).结论 在AD患者中,舌下含服粉尘螨滴剂治疗能降低其外周血IL-4、IL-17,升高IFN-γ和Treg水平而达到治疗的目的.     

脑心通胶囊调节急性脑梗死患者Th17/Treg平衡及相关细胞因子水平的价值

目的分析脑心通胶囊调节急性脑梗死患者辅助性T细胞17/调节性T细胞(Th17/Treg)平衡及相关细胞因子水平的价值。方法选取该院2016年2月至2018年5月收治的急性脑梗死患者104例,根据治疗方法不同分为对照组(n=52)和观察组(n=52)。对照组采用抗凝、降脂等对症治疗,观察组在对照组基础上联合脑心通胶囊治疗,分析2组患者治疗后的临床疗效。结果观察组总有效率为90.38%,对照组为73.08%,观察组患者总有效率高于对照组,差异有统计学意义(P0.05)。2组治疗前Th17比例、Treg比例、Th17/Treg、肽素、超敏C-反应蛋白(hs-CRP)、血管生成素-2(Ang-2)水平组间比较,差异无统计学意义(P0.05)。观察组治疗后Treg比例、Ang-2高于对照组,Th17比例、Th17/Treg、肽素、hs-CRP水平低于对照组(P0.05)。2组治疗前简易智力状态量表(MMSE)评分、日常生活能力量表(ADL)评分组间比较,差异无统计学意义(P0.05)。观察组治疗后MMSE评分、ADL评分高于对照组,差异有统计学意义(P0.05)。结论脑心通胶囊可调节急性脑梗死患者外周血Th17/Treg平衡,降低肽素、hs-CRP的表达,提高Ang-2的表达,改善患者认知功能和生活能力。     

外周血辅助性T细胞17与调节性T细胞的平衡与白癜风临床特征的相关性

目的分析白癜风患者外周血辅助性T细胞17(Th17)与调节性T细胞(Treg)的平衡与临床特征的关系。方法选取白癜风患者109例,其中进展期患者56例,稳定期患者53例,另选取同期本院健康体检者59例为对照组。采用流式细胞术检测3组受试者外周血Th17、Treg细胞数量;采用酶联免疫吸附法(ELISA)检测3组受试者白介素-17(IL-17)、叉头盒蛋白P3(Foxp3)水平;采用Pearson法分析白癜风患者Th17、Treg细胞及IL-17、Foxp3的关系。结果对照组、稳定期组、进展期组Th17细胞含量、Th17/Treg、IL-17水平逐渐升高,Treg细胞含量、Foxp3水平逐渐降低,差异有统计学意义(P0.05)。随着白癜风皮损面积的增加,Th17细胞含量、Th17/Treg、IL-17水平逐渐升高,Treg细胞含量、Foxp3水平逐渐降低,差异有统计学意义(P0.05)。白癜风患者Th17细胞与Treg细胞、IL-17与Foxp3均呈显著负相关(r=-0.449、-0.497,P0.05)。结论 Th17/Treg细胞平衡可能与白癜风的发生及临床特征有关。     

高压氧治疗溃疡性结肠炎患者的疗效及对Th17/Treg细胞免疫调节的影响

目的 探讨高压氧治疗溃疡性结肠炎（UC）患者的疗效及其对外周血Thl7细胞（CD4＋ IL-17＋T细胞）与Treg细胞（CD4＋ CD25＋T细胞）数量的影响.方法 选择74例UC患者,随机分为柳氮磺胺吡啶组（对照组）38例和高压氧联合柳氮磺胺吡啶组（高压氧组）40例.治疗4周后,比较2组总有效率,同时采用流式细胞仪检测治疗前后CD4＋ IL-17＋T细胞与CD4＋CD25＋T细胞的表达百分比.结果 2组患者在治疗前外周血Thl7细胞所占比例、Treg细胞所占比例、Th17/Treg细胞的比值差异均无统计学意义（t=1.747,0 149,0 091,P＞0.05）.治疗后,2组患者外周血Thl7细胞所占比例均明显下降（t=14.679,17.486,P＜0.01）,Treg细胞所占比例均明显升高（t=9.85,13.042,P＜0.01）,而Th17/Treg细胞的比值则下降（t=12.5,9.09,P＜0.01）.高压氧组Thl7细胞所占比例下降程度、Treg细胞所占比例升高程度以及Th17/Treg细胞的比值下降程度较对照组更为明显（t=9.076,8.638,2.227,P＜0.05）.结论 Th17/Treg失衡可能参与UC的发生发展,而HBO联合柳氮磺胺吡啶正是通过调节Th17/Treg的失衡关系,改善免疫抑制功能,抑制炎症因子的释放来达到抗炎-促炎平衡的治疗作用,这可能是其治疗UC的免疫调节重要机制之一.     

美沙拉嗪联合双歧杆菌三联活菌治疗溃疡性结肠炎疗效及对患者肠黏膜屏障功能和血清炎症因子的影响

目的探讨美沙拉嗪联合双歧杆菌三联活菌治疗溃疡性结肠炎(UC)疗效及对患者肠黏膜屏障功能和血清炎症因子的影响。方法筛选88例UC患者,按照随机数表法分为观察组和对照组各44例。对照组给予美沙拉嗪口服,观察组同时给予双歧杆菌三联活菌口服。比较两组临床疗效及治疗前后免疫功能指标、肠黏膜屏障功能指标和血清炎症因子水平。结果观察组治疗总有效率高于对照组(P0.05);治疗后两组免疫功能指标、肠黏膜屏障功能指标和血清炎症因子水平均有改善,而观察组改善更显著(P0.05);两组不良反应发生率比较,差异无统计学意义(P 0.05)。结论双歧杆菌三联活菌联合美沙拉嗪可发挥协同作用,提高临床疗效,明显改善UC患者的免疫功能及肠黏膜屏障功能,减轻炎症反应损伤。     

寿胎丸治疗对反复自然流产患者Th17/Treg细胞表达水平的影响

目的 探讨寿胎丸治疗对反复自然流产(RSA)患者调节性T细胞(Treg)和辅助性T细胞17(Th17)表达水平的影响.方法 流式细胞术检测20例RSA患者寿胎丸治疗前及治疗1、3个月后外周血Th17、Treg细胞表达水平,以26例健康孕妇作为对照组.结果 RSA患者Th17细胞表达水平显著升高(P＜0.05),Treg表达水平显著降低(P＜0.05).治疗3个月后,RSA患者Th17细胞数量降低(P＜0.05),Treg细胞数量升高(P＜0.05);治疗前Th17/Treg比值高于对照组(P＜0.05),治疗后逐渐降低,3个月后恢复至正常水平.结论 Th17和Treg细胞参与了RSA免疫应答,Th17/Treg细胞平衡在维持妊娠中发挥重要作用.寿胎丸可有效改善RSA患者Th17/Treg细胞失衡.     

急性缺血性脑卒中患者外周血Th17/Treg细胞亚群 水平的变化及临床意义

目的：探讨外周血辅助性T细胞-17（Th17）/调节性T细胞（Treg）细胞亚群在急性缺血性脑卒中（AIS） 患者的水平变化及临床意义。方法：符合纳入标准的AIS患者190例纳入观察组,健康体检者60例纳入对 照组;根据美国国立卫生院脑卒中量表（NIHSS）评分将观察组分为轻度亚组61例,中度亚组64例,重度亚 组65例;根据mRS评分纳入预后良好亚组139例,纳入预后不良亚组51例。采用流式细胞仪检测并比较各 （亚）组外周血Th17/Treg细胞水平,酶联免疫吸附法检测并比较相关细胞因子（IL-17,TGF-β）;评价Th17/ Treg 细胞亚群水平对 AIS 患者预后不良的预测价值。结果：观察组患者外周血 Th17、Th17/Treg 比值及 IL-17 水平明显高于对照组（P＜0.05）,Treg 细胞亚群和 TGF-β水平显著低于对照组（P＜0.05）。外周血 Th17、Th17/Treg比值及IL-17水平比较,重度亚组最高,中度亚组次之,轻度亚组最低（P＜0.05）;Treg细胞 亚群和TGF-β水平比较,重度亚组最低,中度亚组次之,轻度亚组最高（P＜0.05）。预后不良组患者外周血 Th17、Th17/Treg比值及IL-17水平明显高于预后良好组（P＜0.05）,Treg细胞亚群和TGF-β水平显著低于预 后良好组（P＜0.05）。ROC曲线分析显示,外周血Th17细胞和Treg细胞水平对AIS患者预后不良预测的敏 感性分别为78.01%和79.17%,特异性分别为82.50%和74.50%。结论：外周血Th17/Treg细胞亚群与AIS的 病情严重程度及预后密切相关,对于AIS患者病情严重程度及预后的评估,具有一定的临床应用价值。     

寻常型白癜风与晕痣患者外周血T淋巴细胞亚群及Th1/Th2、Th17/Treg细胞平衡比较

目的比较寻常型白癜风与晕痣患者外周血辅助性T细胞1(Th1)、Th2、Th17、调节性T淋巴细胞(Treg细胞)水平,以及Th1与Th2比值(Th1/Th2)、Th17与Treg比值(Th17/Treg)。方法选取43例进展期寻常型白癜风患者和37例Ⅰ、Ⅱ阶段晕痣患者进行研究,均采集外周血进行流式细胞学检测。对照组(n=15)为本院常规体检健康人群。结果寻常型白癜风组病灶多部位者比率显著高于晕痣组多部位者比率(P 0.05)。寻常型白癜风组、晕痣组及对照组Th2、Th17细胞水平及Th17/Treg有显著差异(P 0.05),Th1、Treg细胞及Th1/Th2无显著差异(P 0.05)。结论寻常型白癜风与晕痣患者外周血Th1、Th2、Th17及Treg细胞变化存在差异,表现为寻常型白癜风患者外周血Th17细胞增高更为显著,而晕痣患者外周血Th2细胞下降更显著。     

胃肠安丸联合双歧杆菌三联活菌胶囊治疗溃疡性结肠炎的疗效分析

目的 探究胃肠安丸与双歧杆菌三联活菌胶囊联用对溃疡性结肠炎(UC)的临床疗效。方法 选取2017年6月～2020年6月我院收治的80例UC患者,随机分为对照组和观察组各40例。对照组应用双歧杆菌三联活菌胶囊治疗,在此基础上,观察组加用胃肠安丸治疗。比较两组治疗前、治疗3个月时T淋巴细胞亚群(CD4+、CD8+、CD4+/CD8+)及中医症候积分。结果 治疗3个月,两组CD4+、CD8+、CD4+/CD8+水平显著升高,中医症候积分(腹泻、血便、腹痛)显著降低,且观察组改善程度显著优于对照组,差异有统计学意义(P0.05)。结论 胃肠安丸与双歧杆菌三联活菌胶囊联用可提高UC的治疗效果,增强患者免疫功能,减轻患者临床症状。     

Tim-3在多发性骨髓瘤患者Th17/Treg细胞失衡中的意义

目的:探讨Tim-3在多发性骨髓瘤(MM)患者Th17/Treg失衡中的意义。方法:选取56例初诊MM患者及30例健康者,采用流式细胞术检测两组外周血CD4^+T细胞上Tim-3的表达、Th17和Treg细胞各占比例、Th17/Treg比值、Tim-3在Th17及Treg细胞上的表达、Tim-3^+Th17/Tim-3^+Treg比值。运用ELISA技术检测细胞因子IL-17和IL-10的水平。分析Tim-3^+Th17/Tim-3^+Treg平衡与临床指标的关系。结果:与对照组相比,MM患者外周血CD4^+T细胞上Tim-3表达明显增高(P<0.05)。MM患者组Th17细胞比例、Th17/Treg比值较对照组明显增高(P<0.05),MM患者Treg细胞比例较对照组低,差异无统计学意义(P>0.05)。MM患者组细胞因子IL-17、IL-10及IL-17/IL-10比值均较对照组明显增高(P<0.05)。MM患者组Tim-3^+Th17细胞水平及Tim-3^+Th17/Tim-3^+Treg比例较对照组明显增高(P<0.05),MM患者Tim-3^+Treg细胞水平较对照组低,差异有统计学意义(P<0.05)。MM患者Tim-3^+Th17/Tim-3^+Treg比值与ISS分期、DS分期、染色体异常及sFLCR呈正相关(r=0.635、r=0.501、r=0.449、r=0.587)。结论:MM患者体内存在Th17/Treg、IL-17/IL-10及Tim-3^+Th17/Tim-3^+Treg比值增高,其中Tim-3^+Th17/Tim-3^+Treg比值与患者ISS分期、DS分期、染色体异常及sFLCR有关,提示Tim-3参与了MM患者Th17/Treg失衡。     

T cell proliferation induced by anti-self-I-A-specific T cell hybridomas. Evidence of a T cell network

Allo-I-A-reactive T cell hybridomas were generated from MLR-activated lymphoblasts. Cloned hybridomas T1.203, T1.321, and T1.426 were stimulated by I-Ab determinants, as shown by their ability to secrete IL-2 in response to a panel of MHC-recombinant mice. T2.146, T2.205, and T3.116 were found to be specific for I-Ak determinants using a similar panel of MHC-recombinant mice. Inhibition of IL-2 secretion by anti-I-A mAb confirmed these data. Some I-Ab-specific hybrids stimulated the proliferation of T cells from C57BL/6 (H-2b) mice. Similarly, some I-Ak-specific hybrids stimulated the proliferation of T cells from C3H/HeJ (H-2k) mice. These hybrids expressed no detectable surface I-A, and stimulation of T cells was not inhibited by anti-I-A mAb. These results are consistent with the hypothesis that normal mice possess a population of T cells responsive to idiotypic determinants on anti-MHC class II T cell receptors.     

T regulatory cell chemokine production mediates pathogenic T cell attraction and suppression

T regulatory cells (Tregs) control immune homeostasis by preventing inappropriate responses to self and nonharmful foreign antigens. Tregs use multiple mechanisms to control immune responses, all of which require these cells to be near their targets of suppression; however, it is not known how Treg-to-target proximity is controlled. Here, we found that Tregs attract CD4⁺ and CD8⁺ T cells by producing chemokines. Specifically, Tregs produced both CCL3 and CCL4 in response to stimulation, and production of these chemokines was critical for migration of target T cells, as Tregs from Ccl3^–/– mice, which are also deficient for CCL4 production, did not promote migration. Moreover, CCR5 expression by target T cells was required for migration of these cells to supernatants conditioned by Tregs. Tregs deficient for expression of CCL3 and CCL4 were impaired in their ability to suppress experimental autoimmune encephalomyelitis or islet allograft rejection in murine models. Moreover, Tregs from subjects with established type 1 diabetes were impaired in their ability to produce CCL3 and CCL4. Together, these results demonstrate a previously unappreciated facet of Treg function and suggest that chemokine secretion by Tregs is a fundamental aspect of their therapeutic effect in autoimmunity and transplantation.     

Downregulation of T cell responses by antibodies to the T cell receptor

We have derived a T cell clone that recognizes and responds to three different types of antigen: self + X (fowl gamma globulin + H-2d), allo-H-2p,b, and minor lymphocyte-stimulating (Mlsa,d) determinants. Anti-TcR mAb and their F(ab')2 and Fab fragments were tested for their capacity to block the response of this clone. When responses were assayed on day 4 or later, addition of KJ16 or F23.1 mAb caused a marked inhibition of the response to each of the three antigens recognized by the clone. Responses measured at earlier time points however were unaffected or enhanced. This finding suggested that the inhibitory effects of anti-TcR mAb that followed the phase of enhancement might have reflected downregulation of the cells rather than simple blockade of TcR. In support of this possibility it was found that addition of anti-TcR mAb caused marked inhibition of the response of the clone to IL-2, i.e., a response that is not known to involve the TcR.     

Phosphoinositide 3-kinase gamma participates in T cell receptor-induced T cell activation

Class I phosphoinositide 3-kinases (PI3Ks) constitute a family of enzymes that generates 3-phosphorylated polyphosphoinositides at the cell membrane after stimulation of protein tyrosine (Tyr) kinase-associated receptors or G protein-coupled receptors (GPCRs). The class I PI3Ks are divided into two types: class I(A) p85/p110 heterodimers, which are activated by Tyr kinases, and the class I(B) p110gamma isoform, which is activated by GPCR. Although the T cell receptor (TCR) is a protein Tyr kinase-associated receptor, p110gamma deletion affects TCR-induced T cell stimulation. We examined whether the TCR activates p110gamma, as well as the consequences of interfering with p110gamma expression or function for T cell activation. We found that after TCR ligation, p110gamma interacts with G alpha(q/11), lymphocyte-specific Tyr kinase, and zeta-associated protein. TCR stimulation activates p110gamma, which affects 3-phosphorylated polyphosphoinositide levels at the immunological synapse. We show that TCR-stimulated p110gamma controls RAS-related C3 botulinum substrate 1 activity, F-actin polarization, and the interaction between T cells and antigen-presenting cells, illustrating a crucial role for p110gamma in TCR-induced T cell activation.     

Partially phosphorylated T cell receptor zeta molecules can inhibit T cell activation

The T cell receptor complex (TCR) zeta chain is constitutively tyrosine phosphorylated specifically at two of the six zeta immunoreceptor tyrosine-based activation motif (ITAM) tyrosine residues in resting peripheral T cells. Further phosphorylation of zeta is induced by both agonist and antagonist ligands of the TCR, with agonists inducing complete phosphorylation of the zeta ITAM tyrosines. After antagonist stimulation, zeta phosphorylation is incomplete and generates discrete forms of partially phosphorylated ITAMs. Here, we mutate specific tyrosines in chimeric human CD8-zeta molecules to reflect phosphorylation in resting T cells as well as phosphorylation induced by agonist and antagonist ligands. We demonstrate that such partially phosphorylated TCR-zeta species can inhibit IL-2 production in T cell hybridomas and proliferation in T cell clones. This reveals a previously unrecognized, inhibitory function of partially phosphorylated ITAMs. These findings support the concept that TCR antagonism can arise through the generation of an inhibitory signal within the TCR complex and that constitutive zeta phosphorylation in resting T cells is an inhibitory signaling environment.     

T cell traffic signals

In 1990, Charles Mackay and colleagues combined classical physiology with modern molecular biology to provide the first concrete evidence that naive and memory T cells follow distinct migratory routes out of the bloodstream--a discovery that helped invigorate the field of lymphocyte homing.     

Cutaneous T cell lymphoma

Cutaneous T cell lymphoma is a malignancy of helper T cells, which have a propensity to infiltrate the skin. The incidence of the disease appears to exceed that of Hodgkin's disease, making it the most common lymphoma of adults. Advances in our knowledge of the biology of the malignant T cells should facilitate new and more effective forms of treatment.     

Protease inhibitors selectively block T cell receptor-triggered programmed cell death in a murine T cell hybridoma and activated peripheral T cells

The hypothesis that cytoplasmic proteases play a functional role in programmed cell death was tested by examining the effect of protease inhibitors on the T cell receptor-mediated death of the 2B4 murine T cell hybridoma and activated T cells. The cysteine protease inhibitors trans-epoxysuccininyl-L-leucylamido-(4-guanidino) butane (E-64) and leupeptin, the calpain selective inhibitor acetyl-leucyl-leucyl- normethional, and the serine protease inhibitors diisopropyl fluorophosphate and phenylmethylsulfonyl fluoride, all showed dose- dependent blocking of the 2B4 death response triggered by the T cell receptor complex and by anti-Thy-1. These protease inhibitors enhanced rather than inhibited IL-2 secretion triggered by T cell receptor cross- linking, showing that they did not act by preventing signal transduction. Growth inhibition induced by cross-linking the 2B4 T cell receptor, measured by inhibition of thymidine incorporation, was not generally blocked by these protease inhibitors. All five of these protease inhibitors enhanced rather than blocked 2B4 cell death triggered by dexamethasone, an agent previously shown to have a death pathway antagonistic with that of the TCR. 2B4 cytolysis by the cytotoxic agents staphylococcal alpha-toxin and dodecyl imidazole, and that caused by hypotonic conditions, was not significantly affected by the five protease inhibitors tested. The selected protease inhibitors blocked both the apoptotic nuclear morphology changes and DNA fragmentation induced by T cell receptor cross-linking, and enhanced both these properties induced by dexamethasone in 2B4 cells. The T cell receptor-induced death of activated murine lymph node T cells and human peripheral blood CD4+ T cells was blocked by both cysteine and serine protease inhibitors, showing that the protease-dependent death pathway also operates in these systems.