结合脂蛋白肽136-150修饰抗原肽与实验性变态反应脑脊髓炎

目的　观察结合脂蛋白肽 136 15 0 (PLP136 15 0 )修饰抗原肽是否具有引起脑脊髓炎(EAE)的可能性。方法　用 2 0 0 μgPLP136 15 0修饰抗原肽分组免疫SJL/J雌性小鼠 ,诱导主动EAE。对未发生主动EAE组小鼠再用已免疫抗原 5 0 μg重复接种 1次 ,继而建立短期T细胞株。用PLP136 15 0或修饰抗原肽 2 0 μg/ml分别刺激T细胞并将得到的T淋巴母细胞转移给同种小鼠 [(1～ 2 )× 10 7/鼠 ]以诱发被动EAE。结果　在 2 2个一位氨基酸被替换的修饰抗原肽中除 144A、K外 ,2 0个均成功诱发主动EAE ,一位氨基酸变异的 144A、K ,及双位 (143A/ 145A ,145A/ 148K)和三位 (139A/ 144A/ 148A)氨基酸被替换的修饰抗原虽不能引起主动EAE ,但若将这些抗原诱导、建立并刺激的T细胞株转移给同种小鼠可引起被动EAE ,而接受PLP136 15 0刺激的同种T细胞的小鼠不发生被动EAE。结论　修饰抗原肽仍具有诱发EAE的潜在可能性     

CD4~+ T细胞和小胶质细胞在实验性自身免疫性脑脊髓炎中的作用

实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)是在动物体内诱导的神经系统慢性脱髓鞘性疾病。EAE的临床表现和病理改变与多发性硬化症(multiple sclerosis,MS)极为相似,是研究MS理想的动物模型。近年来已有研究发现EAE主要是由自身反应性CD4+T细胞介导的自身免疫性脱髓鞘疾病,在EAE动物发病的不同阶段CD4+T细胞和小胶质细胞数量、形态和表型的改变对疾病的进展起重要作用。通过对EAE病理中CD4+T细胞和小胶质细胞的研究,将有助于进一步了解MS的免疫病理特征及发病机制,为MS的治疗和预防奠定基础。     

MOG诱导小鼠实验性自身免疫性脑脊髓炎及其对CD4+CD25+调节性T细胞的影响

目的： 探讨采用分子克隆技术诱导表达出的含硫氧还蛋白基团的髓鞘少突胶质细胞糖蛋白细胞外Ig样结构域(MOGIgd-TrxA)融合蛋白免疫C57BL/6小鼠,建立多发性硬化的动物模型实验性自身免疫性脑脊髓炎的可行性;通过检测模型小鼠脾脏中CD4+CD25+调节性T细胞的数量,初步探讨CD4+CD25+调节性T细胞在实验性自身免疫性脑脊髓炎发病机制中的作用。方法: (1)分子克隆技术合成MOGIgd-TrxA融合蛋白,纯化、超滤浓缩后Bradford法测定蛋白浓度。(2)动物实验:C57BL/6小鼠,随机分为4组：MOGIgd-TrxA组（MOG组）、豚鼠脊髓匀浆组、硫氧还蛋白（TrxA）组及生理盐水正常对照组,每组动物12只,各组以相应抗原乳剂免疫小鼠制作EAE模型后评估其临床神经功能、组织病理(HE染色和髓鞘luxol fast blue染色)并评价模型质量。(3)流式细胞仪(FACS)检测小鼠脾脏中CD4+CD25+调节性T细胞的百分比。结果:(1)纯化浓缩后MOGIgd-TrxA蛋白纯度达98%左右,浓度约2.3 g/L。(2)MOG组小鼠与豚鼠脊髓匀浆组小鼠在临床神经功能评分等方面无显著差异(P>0.05)。2组发病动物组织切片HE染色和髓鞘染色均有不同程度的病理改变。(3)CD4+CD25+调节性T细胞占CD4+T细胞比例MOG组为(4.71±1.61)％,豚鼠脊髓匀浆组为(1.44±0.65)％,均明显低于生理盐水正常对照组（9.22±1.24）％和硫氧还蛋白（TrxA）组（8.97±1.20）％(P<0.01)。结论: (1)分子克隆技术合成的MOGIgd蛋白免疫C57BL/6小鼠能够成功诱导出EAE模型,且模型稳定、发病率高,为进一步研究MS免疫发病机制并采取有效治疗措施奠定基础;(2)CD4+CD25+调节性T细胞数量减少可能与EAE小鼠临床表现相关。     

外源性髓鞘抗原的清除在实验性自身免疫性脑脊髓炎中的作用

目的探讨外源性髓鞘抗原的清除对其诱导实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis, EAE)的作用。方法用髓鞘少突胶质细胞糖蛋白35～55肽(myelin oligodendrocyte glycoprotein 35-55, MOG35-55)或FITC标记的MOG35-55免疫C57BL/6J小鼠诱导EAE, 通过分析过继转移的CFSE标记的mT/mG-2D2 CD4+T细胞在脾脏内的增殖情况评估免疫系统内外源性髓鞘抗原的含量;免疫组织化学法和流式细胞术分析接种部位外源性髓鞘抗原的释放;组织切片HE染色探讨外源性髓鞘抗原快速清除的原因;通过对比分析背部和足垫免疫诱导的EAE, 以及可溶性MOG35-55的治疗效果验证外源性髓鞘抗原的清除在EAE中的作用。结果免疫第2天小鼠脾脏内mT/mG-2D2 CD4+T细胞增殖占比显著高于免疫第7天[(52.6±6.8)%vs(18.5±4.9)%,P<0.01];在发病小鼠(第13天)脾脏内mT/mG-2D2 CD4+T细胞增殖与在初始小鼠脾脏内的增殖差异无统计学意义[(4...     

B7H4在间充质干细胞C3H10 T1/2移植治疗小鼠实验性变态反应性脑脊髓炎中的作用研究

目的 探讨B7-H4分子在C3H10 T1/2细胞(C3H10)移植治疗小鼠实验性变态反应性脑脊髓炎(EAE)中的作用.方法 ①用慢病毒将B7-H4靶向shRNA转染至C3H10细胞(C3H10-shRNA)并观察其对小鼠脾脏细胞活化增殖的调节作用;②利用MOG35-55和完全弗氏佐剂制备小鼠EAE模型,将50只小鼠分为正常对照组、EAE模型组、C3H10细胞组、C3H10-NC细胞组、C3H10-shRNA细胞组,通过HE染色、Fast-blue染色观察病理学改变,用免疫组化法检测B7-H4表达,结合神经功能评分观察不同干预方式对EAE损伤组织结构和功能的影响.结果 ①下调表达B7-H4的C3H10细胞可使其对小鼠脾细胞的免疫抑制作用减弱;②C3H10移植于EAE小鼠可减少、延缓发病,而移植C3 H 10-shRNA细胞的EAE小鼠发病时间、神经缺损评分和炎性细胞浸润、脱髓鞘改变及B7-H4的阳性细胞数均介于EAE组与其他对照组之间.结论 C3H10细胞移植治疗EAE的安全、有效,B7-H4分子可能通过影响C3H10的免疫调节作用等生物学行为而影响移植疗效.     

γδT细胞在多发性硬化和实验性变态反应性脑脊髓膜炎中的作用

多发性硬化（multiple sclerosis,MS）是一种十分常见的中枢神经系统的自身免疫性疾病,特征性的血管周CD4^＋T细胞和单核细胞浸润会导致脱髓鞘反应,引起渐进性的瘫痪。在急性脱髓鞘MS病人的硬化斑块中可以检测到γδT细胞的存在,分离MS患者硬化斑块中的γδT细胞进行体外培养会导致Vδ1和Vδ2 γδT细胞的扩增。研究发现,只有从急性起病患者体内分离的γδT细胞才可以扩增,     

Irgm1基因敲除对实验性自身免疫性脑脊髓炎小鼠CD4~+ T细胞亚群的影响

目的:探讨免疫相关GTP酶1(Irgm1)基因敲除对实验性自身免疫性脑脊髓炎(Experimental autoimmune encephalomyelitis,EAE)小鼠CD4+T细胞的影响。方法:C57BL/6纯系小鼠与Irgm1基因敲除杂合小鼠(Irgm1+/-)回交十代繁殖C57BL/6背景下Irgm1+/-小鼠,用C57BL/6 Irgm1+/-小鼠杂交获取Irgm1-/-、Irgm1+/-、Irgm1+/+三种基因型小鼠,PCR扩增DNA检测基因型。用髓鞘少突胶质糖蛋白(Myelin oligodendrocyte glycoprotein,MOG33-55)多肽与弗氏完全佐剂等量混合制成乳剂,免疫C57BL/6野生型(Wt.)和Irgm1基因敲除(Irgm1-/-)小鼠,建立EAE模型,并进行临床评分。MTT法测定MOG33-55免疫后7 d的EAE小鼠淋巴结细胞中MOG33-55特异性T细胞增殖分化水平。取MOG33-55免疫后14 d EAE小鼠脊髓切片,HE染色检测炎细胞浸润情况。取MOG33-55免疫后16 d的EAE-小鼠淋巴结、脊髓和脑组织,提取单个核细胞,用MOG33-55(20μg/ml)体外刺激培养7 d,收集细胞,用流式细胞仪分析EAE小鼠淋巴结、中枢神经系统浸润细胞中Th1、Th17的改变。结果:成功诱导了EAE小鼠模型;HE染色结果显示Wt.小鼠脊髓周围出现明显炎细胞浸润,而Irgm1-/-小鼠则无明显变化;MTT实验表明Irgm1-/-小鼠与Wt.小鼠相比,淋巴结中T细胞对MOG33-55特异性增殖能力降低;流式细胞分析表明相对于Wt.小鼠,Irgm1-/-小鼠EAE模型在淋巴结及中枢神经系统浸润细胞中Th1细胞亚群比例明显增高而Th17细胞亚群比例下降。结论:Irgm1基因敲除可部分保护EAE小鼠的脊髓功能及临床症状。在EAE发病早期,Irgm1可能起到了关键性的作用,因此Irgm1有可能成为EAE治疗的重要分子靶点。     

MOG诱导的实验性自身免疫性脑脊髓炎小鼠中枢及外周神经系统CD4~+ T及CD8~+ T调节性细胞变化

目的:观察实验性自身免疫性脑脊髓炎小鼠中枢及外周CD4+ CD25+调节性T细胞(CD4+ CD25+ Treg),CD8+ CD28-调节性T细胞(CD8+ CD28- Treg)表达的变化情况,并探讨相关的细胞免疫学机制。方法:雌性C57BL/6小鼠随机分为未使用髓鞘少突胶质细胞糖蛋白35-55(MEVGWYR-SPFSRVVHLYRNGK)(MOG35-55)免疫的对照组和使用MOG35-55免疫诱导的EAE小鼠模型组,采用临床症状评分记录小鼠行为学变化、HE染色观察CNS炎症细胞浸润及病理改变,使用流式细胞术(FCM)检测小鼠中枢及外周CD8+ CD28- Treg,CD4+ CD25+ Treg细胞表达水平。结果:MOG35-55诱导的EAE模型组动物出现典型的EAE临床行为学及病理学表现,FCM检测EAE模型组小鼠脾细胞CD4+ CD25+ Treg较对照组升高但无统计学差异,CD8+ CD28- Treg表达水平明显低于对照组(P0.01),EAE模型组中枢有CD4+ CD25+ Treg,CD8+CD28-Treg淋巴细胞的浸润,且CD4+ CD25+ Treg,CD8+ CD28- Treg在中枢的表达均高于外周,对照组中枢神经系统未检测到淋巴细胞浸润。结论:CD4+ CD25+ Treg,CD8+ CD28- Treg均参与调控EAE的病理过程,CD4+ CD25+ Treg,CD8+ CD28- Treg在EAE小鼠中枢及外周分布及变化的不同,提示其进入中枢神经系统(CNS)并参与调节中枢局部炎症。     

黄芪甲苷对实验性自身免疫性脑脊髓炎小鼠T细胞免疫调节的影响

背景：多发性硬化初始阶段,中枢免疫细胞激活并释放大量炎症因子,引起白质脱髓鞘甚至累及灰质神经元。CD4⁺T细胞不同亚群之间的分化平衡在实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)的病程进展中发挥着重要作用。课题组前期研究结果表明黄芪内有效成分黄芪甲苷能够调节EAE小鼠体内免疫反应,其是否对T细胞亚群分化具有调节作用尚未明确。目的：探究黄芪甲苷对EAE小鼠治疗效果及其对T细胞的免疫调控机制。方法：将C57BL/6雌性小鼠分为正常对照组、EAE疾病模型组和黄芪甲苷治疗组,每组8只,后2组使用髓鞘少突胶质细胞糖蛋白35-55(MOG35-55)制备EAE模型,免疫后第10-28天,黄芪甲苷治疗组以40 mg/(kg·d)灌胃给药。免疫当天至第28天,记录各组小鼠的体质量及临床评分;免疫后第28天取小鼠脊髓制成冰冻切片行苏木精-伊红染色、固蓝染色观察脊髓病理改变,流式细胞术检测脾脏T细胞亚群百分比,Western blot法检测脊髓组织中γ干扰素、白细胞介素17、白细胞介素6的蛋白表达,ELISA检...     

Modulation of calcium responses by altered peptide ligands in a human T cell clone

To determine whether altered peptide ligands (APL) affect calcium signaling events, we investigated changes in intracellular calcium concentration ([Ca²⁺]_i) in human T cell clone stimulated with either the fully agonistic peptide M12p54 – 68, the partially agonistic analogue E63V or the simple antagonistic analogue E58M. Both E63V and E58M stimulated a Ca²⁺ response in ∼ 40 % of T cells, whereas M12p54 – 68 did so in ∼ 70 % of T cells. The most predominant pattern of a Ca²⁺ increase induced by M12p54 – 68 was a small sinusoidal peak followed by a sustained high response. The most frequent pattern of calcium response induced by E63V was a continuous high response without a preceding sinusoidal peak, whereas that induced by E58M was large with frequent oscillations. Genistein, an inhibitor of the protein tyrosine kinases (PTK), markedly inhibited the wild-type peptide-induced increase in [Ca²⁺]_i, whereas it marginally inhibited the response induced by E63V or E58M. In contrast, GF109203X, a protein kinase C (PKC)-specific inhibitor, markedly inhibited the E63V- or E58M-induced Ca²⁺ response, whereas it marginally affected the wild peptide-induced Ca²⁺ response. Furthermore, in nominal Ca²⁺-free medium, the E58M-induced Ca²⁺ response was almost completely blocked, while the M12p54 – 68- or E63V-induced responses were only partially inhibited. Our results suggest that the Ca²⁺ response induced by the fully agonistic peptide depends on activation of the genistein-sensitive signaling pathway, including PTK, whereas the Ca²⁺ response to a simple antagonistic APL completely depends on extracellular Ca²⁺ and activation of the GF109203X-sensitive signaling pathway, including PKC. These differences in the CA²⁺_i response in recognition of different APL may parallel the unique T cell activation patterns induced by APL in human T cells.     

Altered peptide ligands and wild-type peptide induce indistinguishable responses of a human Th0 clone

The response of the human influenza hemagglutinin (HA)-specific T helper clone HA1.7 to its wild-type (wt) HA307 – 319 peptide ligand and related altered peptide ligands (APL) was examined over a wide range of antigen concentrations. The time course of cytokine production and surface expression of CD40 ligand and CD3 was followed at the single-cell level by flow cytometry and compared with the induction of proliferation. We observed that the APL induced responses that were indistinguishable from those induced by the wt HA ligand, albeit at higher antigen densities. Moreover, the activation parameters were induced with identical kinetics. Blocking of CD4 co-ligation inhibited the recognition of the weakly stimulatory APL, but not of the wt HA307 – 319 peptide. Finally, in all cases the response of the T cell clone correlated with down-regulation of surface TCR/CD3 complexes. Together, these observations support a quantitative model of T cell activation.     

Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95 116 as an HLA-DR2,w15-associated determinant

Multiple sclerosis (MS) is a putative autoimmune disease thatis linked with HLA-DR2,w15. Proteollpid protein (PLP) is a candidateautoantigen in MS, but the disease-associated epitopes havenot been determined. Using overlapplng and non-overlapping PLPpeptides, we have studied the T cell response to the major hydrophllicdomain PLP 85–159 in the peripheral blood of MS and healthysubjects (HS). Short-term T cell lines (TCL) were selected againsteach peptide using microwell plates and the frequency of peptide-specificTCL was estimated. PLP 95–116-specific TCL were most efficientlygenerated and the frequency was significantly higher in MS comparedwith HS (P <0.05). When compared between DR2,w15⁺ and DR2,w15^–MS, TCL frequency to PLP 95–116 was significantly higherin DR2,w15⁺ MS (P<0.005) and TCL reactive to the overlappingpeptide 105–124 were also increased in DR2,w15⁺ MS (P<0.025). Using DR gene-transfected L cells, we could show thatthe DRB1^*1501 product of the DR2 haplotype presents PLP 95–116to TCL selected against the pepide. These results imply thatPLP 95–116 represents a major epitope for the DR2,w15⁺MS.     

Aberrant methylation of p14(ARF), p15(INK4b) and p16(INK4a) genes and location of the primary site in pulmonary squamous cell carcinoma

Aberrant methylation of cytosines in CpG islands of the promoter regions of tumor suppressor genes is found in human tumors as a common mechanism of gene silencing. We investigated the methylation status of the chromosome 9p21 gene cluster (p14(ARF), p15(INK4b) and p16(INK4a) genes) by methylation-specific polymerase chain reaction in 20 central and 40 peripheral types of pulmonary squamous cell carcinoma (SqCC) in order to determine the differences between the pathogeneses of the central and peripheral types of SqCC. The frequencies of methylation were 30% for the p14(ARF) gene, 20% for the p15(INK4b) gene and 40% for the p16(INK4a) gene in the central type and 25% for the p14(ARF) gene, 10% for the p15(INK4b) gene and 38% for the p16(INK4a) gene in the peripheral type. Cases in which there was methylation of the p16(INK4a) gene had a higher smoking index in the peripheral type (P = 0.007). This trend was not detected in the central type. Methylation of two or three genes was observed in 55% of methylation in at least one gene of the central type but in only 17% of the peripheral type. This overlap methylation of the chromosome 9p21 gene cluster was found more frequently in the central type (P = 0.02). These findings suggest one of the epigenetic differences between the central and peripheral types of SqCC.     

Frequent alteration of p16(INK4a)/p14(ARF) and p53 pathways in the round cell component of myxoid/round cell liposarcoma: p53 gene alterations and reduced p14(ARF) expression both correlate with poor prognosis

In myxoid/round cell liposarcoma (MLS/RCLS), the presence of a round cell (RC) component has been reported to correlate with a worse prognosis for the patients. However, little is known about the molecular genetic differences between conventional myxoid (MX) components and RC components in this tumour. The aim of this study was to investigate the possible implications of molecular alterations of G1 to S-phase check-point genes, especially in the RC component. We evaluated the immunohistochemical expression of p53, MDM2, p14 and p16 protein and assessed proliferative activities using MIB-1 in 29 RC components and 81 MX components from 90 cases. Mutation of the p53 gene, amplification of the MDM2 gene, homozygous deletion, methylation status and mutation of the p16(INK4a)/p14(ARF) genes were also investigated, using concordant paraffin-embedded and frozen material. The data were analysed together with clinicopathological factors to assess their prognostic implications in MLS/RCLS. Immunohistochemically, the over-expression of p53 protein (p = 0.01366) and the reduced expression of p14 (p < 0.0001) and p16 (p < 0.0001) proteins were significantly more frequently observed in RC components than in MX components. Reduced expression of p14 protein correlated significantly with hypermethylation of the p14(ARF) gene promoter (p = 0.0176) and over-expression of p53 protein (p = 0.00837). By univariate analysis, reduced expression of p14 and p53 missense mutation were found to reduce the rate of survival significantly (p < 0.05). Multivariate analysis, including clinicopathological factors, revealed that tumour site (p = 0.0251), the presence of an RC component (p = 0.0113), high MIB-1 labelling index (p = 0.0005) and p53 missense mutation (p = 0.0036) were adverse prognostic factors. In MLS/RCLS, reduction of p14 protein expression and p53 mutation were related to poor prognosis. Accordingly, the p14(ARF)/p53 pathway may contribute to the presence of an RC component and malignant progression in this tumour.     

Defects in antigen-driven lymphocyte responses in common variable immunodeficiency (CVID) are due to a reduction in the number of antigen-specific CD4+ T cells.

T cells from patients with CVID have defects that may relate to the failure in vivo of B cell production of antibodies. Antigen-driven responses of T cells from CVID patients and normal subjects have been assessed by measuring DNA synthesis in vitro. Low density cells enriched for antigen-presenting dendritic cells were pulsed with purified protein derivative (PPD) and cultured with autologous T cells. Overall, T cells from CVID patients showed a significantly low mean response to PPD, although non-specific DNA synthesis induced in CVID T cells by IL-2 was within the normal range. However, mean PPD-specific T cell responses in CVID were not restored by IL-2 irrespective of the presence of monocytes. Depletion of CD8+ cells also failed to restore the mean PPD response of CVID CD4+ T cells. Limiting dilution analysis showed that in CVID there was a reduced frequency of antigen-specific cells within the T cell preparations. The mean frequency of the PPD-specific T cells in cultures from patients vaccinated with bacille Calmette-Guérin (BCG) was reduced to 1 in 109,000 T cells compared with 1 in 18,600 T cells in BCG-vaccinated normal donors. These data show that the reduced PPD-specific response in CVID is due to a partial peripheral loss of antigen-specific cells.     

Reversal of experimental allergic encephalomyelitis with non-mitogenic, non-depleting anti-CD3 mAb therapy with a preferential effect on T(h)1 cells that is augmented by IL-4

This study examined whether therapy with a non-mitogenic, non-activating anti-CD3 mAb (G4.18) alone, or in combination with the T(h)2 cytokines, could inhibit induction or facilitate recovery from experimental allergic encephalomyelitis (EAE) in Lewis rats. G4.18, but not rIL-4, rIL-5 or anti-IL-4 mAb, reduced the severity and accelerated recovery from active EAE. A combination of rIL-4 with G4.18 was more effective than G4.18 alone. The infiltrate of CD4(+) and CD8(+) T cells, B cells, dendritic cells, and macrophages in the brain stem was less with combined G4.18 and IL-4 than G4.18 therapy or no treatment. Residual cells had preferential sparing of T(r)1 cytokines IL-5 and transforming growth factor-beta with loss of T(h)1 markers IL-2, IFN-gamma and IL-12Rbeta2, and the T(h)2 cytokine IL-4 as well as macrophage cytokines IL-10 and tumor necrosis factor-alpha. Lymph nodes draining the site of immunization had less mRNA for T(h)1 cytokines, but T(h)2 and T(r)1 cytokine expression was spared. Treatment with G4.18, rIL-4 or rIL-5 from the time of immunization had no effect on the course of active EAE. MRC OX-81, a mAb that blocks IL-4, delayed onset by 2 days, but had no effect on severity of active EAE. G4.18 also inhibited the ability of activated T cells from rats with active EAE to transfer passive EAE. This study demonstrated that T cell-mediated inflammation was rapidly reversed by a non-activating anti-CD3 mAb that blocked effector T(h)1 cells, and spared cells expressing T(h)2 and T(r)1 cytokines.     

Effects of interleukin (IL)-13 on immediate-early response gene expression,phenotype and differentiation of human mast cells. Comparison with IL-4

The recently cloned interleukin 13 (IL-13) shares most investigated biological activities on B lymphocytes and monocytes with IL-4. In this study we investigated the potential role of IL-13 in regulating human mast cell activities. The effects of IL-13 on the expression of an immediate-early response gene (c-fos), proliferation, expression of mast cell-associated cell surface antigen (CD54 and Kit), and in vitro differentiation of human mast cells, were investigated. We compared the effect of IL-13 with that of IL-4. Both IL-13 and IL-4 induced expression of c-fos in cells from the human mast cell line HMC-1. This indicates that mast cells express functional receptors for IL-13. IL-13 and IL-4 decreased the proliferation rate of HMC-1 cells. However, IL-13 was less potent than IL-4. Human mast cells constitutively express the adhesion molecule ICAM-1 (CD54) and the receptor for stem cell factor (Kit) (CD117). The expression of CD54 was increased after treatment with IL-13 or IL-4, whereas the expression of Kit was decreased. Also in this action IL-4 was more potent than IL-13. By culturing mononuclear cells from cord blood in the presence of stem cell factor there is a differentiation of tryptase-positive mast cells in the cultures. This process was inhibited when IL-4 was present. In contrast, IL-13 did not affect the expression of tryptase during differentiation of stem cell factor dependent cord blood-derived mast cells. Taken together, these findings indicate that IL-13 has regulatory effects on human mast cells. The effect overlaps with but is also different from that of IL-4.     

CD4 T-cell subsets in autoimmunity

The discovery that functionally heterogeneous CD4⁺ T-cell subsets secrete different cytokines offers an explanation for the ability of certain T cells to mediate a predominant cell-mediated immune response versus a humoral response often accompanied by allergic manifestations. Th1 cells, important for cell-mediated immunity by their production of IL-2, IFN-γ and lymphotoxin, have been implicated in the immunopathology of certain organ-specific autoimmune diseases whereas a role as regulators has been suggested for IL-4 and IL-10 producing Th2 cells. Recent findings, however, beg re-evaluation of the direct role of Th2 cells in the induction or maintenance of tolerance, whereas evidence for the role of a distinct subset of regulatory T cells producing TGF-β to suppress cell-mediated immunopathology is compelling.