Th1, Th2 and Th3 cytokine alteration in schizophrenia

BACKGROUND: Several studies have shown that there is an imbalance between T helper 1 (Th1) cytokines and T helper 2 (Th2) cytokines in patients with schizophrenia. The T helper 3 (Th3) cytokine, transforming growth factor beta-1 (TGF-beta1), has been shown to suppress the production of Th1 cytokines. Therefore it is hypothesized that it may play a role in schizophrenia by suppressing overactive Th1 system. METHODS: We recruited 88 schizophrenic patients and 88 matched controls. The basal plasma concentrations of IFN-gamma (Th1), IL-4 (Th2) and TGF-beta1 (Th3) were studied at the time the patients were admitted to the hospital and following 8 weeks of treatment with antipsychotics. RESULTS: The detection rate of plasma IFN-gamma and basal plasma TGF-beta1 level were significantly higher in schizophrenic patients than in controls whereas detection rate of plasma IL-4 was lower in patients. The ratio of Th1/Th2 cytokines (IFN-gamma/IL-4) was higher in schizophrenic patients. Following the neuroleptic treatment, the IFNgamma and TGF-beta1 levels returned to control values, and IL-4 concentration rose above the control value. CONCLUSION: Schizophrenic patients showed higher Th1/Th2 ratio which is attenuated by effective neuroleptic treatment. It is possible that TGF-beta1 plays a role in reducing the activity of Th1 cytokine.     

Th1 and Th2 serum cytokine profiles characterize patients with Hashimoto's thyroiditis (Th1) and Graves' disease (Th2)

OBJECTIVES: The aim of this study was to document the pattern of immune response, assessed by the measurement of both Th1 and Th2 serum cytokines, in patients suffering from autoimmune thyroid disease and toxic nodular goiter. METHODS: Both Th1 and Th2 serum cytokine levels were assayed in patients suffering from Graves' disease (GD, n = 25), Hashimoto's thyroiditis (HT, n = 21), and toxic nodular goiter (TNG, n = 7) and compared with corresponding levels of 25 healthy controls. Serum concentrations of IL-2, IL-1 beta, INF-gamma, TNF-alpha, IL-12, IL-15, IL-10, IL-18, IL-4 and IL-5 were assayed in fasting serum samples. RESULTS: It was found that patients with HT had higher IL-2 serum levels (12.16 +/- 0.66 pg/ml) compared to patients with TNG (9.25 +/- 0.84 pg/ml), GD (7.86 +/- 0.30 pg/ml) and controls (7.36 +/- 0.45 pg/ml; p = 0.0001), higher INF-gamma levels (7.60 +/- 0.33 pg/ml) compared to patients with TNG (5.77 +/- 0.55 pg/ml), GD (5.74 +/- 0.24 pg/ml) and controls (5.09 +/- 0.27 pg/ml; p = 0.0009), higher IL-12 levels (3.57 +/- 0.19 pg/ml) compared to patients with TNG (2.57 +/- 0.21 pg/ml), GD (2.48 +/- 0.13 pg/ml) and controls (2.59 +/- 0.23 pg/ml; p = 0.004), and higher IL-18 levels (27.52 +/- 1.75 pg/ml) compared to patients with TNG (18.71 +/- 2.24 pg/ml), GD (15.44 +/- 1.39 pg/ml) and controls (15.16 +/- 1.62 pg/ml; p = 0.0002). In contrast, patients with GD had higher serum levels of IL-4 (4.11 +/- 0.33 pg/ml) compared to patients with HT (3.0 +/- 0.16; p = 0.02) and higher IL-5 levels (4.22 +/- 0.30 pg/ml) compared to patients with TNG (3.21 +/- 0.58 pg/ml), HT (2.75 +/- 0.16 pg/ml) and controls (2.0 +/- 0.19 pg/ml; p = 0.0001). Patients had lower IL-1 beta serum levels (TNG 2.45 +/- 0.20, HT 2.52 +/- 0.14, GD 2.68 +/- 0.12 pg/ml) compared to controls (3.6 +/- 0.20 pg/ml; p = 0.008). CONCLUSIONS: The above findings suggest that a Th1 pattern of immune response characteristic of cellular immunity is dominant in HT, whereas the predominance of Th2 cytokines in GD indicates a humoral pattern of immune reaction.     

Epigenetic regulation of Th1 and Th2 cell development

All cells of the body, regardless of the tissue type, contain the same genetic material, but express this genetic material differently. Epigenetics is one process by which differential gene expression within a cell is regulated. Epigenetic mechanisms involve postsynthetic modifications to DNA and/or DNA-associated histones that do not change the DNA sequence itself, but which remodel chromatin, are passed along at each cell division, and occur during and after early development. The CD4⁺ T cell best represents a cell in which epigenetic mechanisms are used to affect mature cell physiology. As a naïve CD4⁺ T cell develops into either a Th1 or Th2 cell that secretes predominantly IFN-γ or IL-4, respectively, the expression of one cytokine gene and the permanent silencing of the other is orchestrated using epigenetic mechanisms. Because there appears to be an association between Th1/Th2 cell immunity, behavior, and/or disease, it is possible that an environmentally induced epigenetic change that occurs during Th1/Th2 cell development could explain how certain Th1/Th2-associated conditions develop. This article will review basic epigenetic mechanisms and what is known about how these mechanisms influence cytokine gene expression in a naïve CD4⁺ T cell as it develops into a Th1 or Th2 cell.     

重症肌无力患者血清Th1/Th2/Th17细胞因子的变化及意义

目的：分析重症肌无力（MG）患者血清CD4^＋ T细胞主要细胞因子的水平,探讨不同亚型CD4^＋ T细胞分泌的细胞因子在MG发病机制中的作用。方法：用ELISA测定93例MG患者和34名健康对照者血清中各项细胞因子（IL-2、IL-12、IFN-γ、TNF-α、IL-4、IL-10、IL-13和IL-17）的水平,分组行统计学分析。结果：与健康对照组相比,MG患者Th1细胞相关各细胞因子（IL-2、IL-12、IFN-γ及TNF-α）均明显升高,差异有统计学意义（P〈0.05）;Th2细胞相关的细胞因子IL-4、IL-10差异无统计学意义（P〉0.05）,仅IL-13水平升高;Th17细胞的细胞因子IL-17水平差异无统计学意义（P〉0.05）。MG眼肌型与全身型患者血清中各细胞因子水平的差异无统计学意义（P〉0.05）,在不同病程的MG患者中差异也无统计学意义（P〉0.05）。结论：Th1细胞因子在MG发病机制中发挥重要作用,而Th2细胞及其细胞因子在MG机制中的角色各异。     

Coemergence of insomnia and a shift in the Th1/Th2 balance toward Th2 dominance

OBJECTIVES: Insomnia is associated with physical and mental disorders. We examined the effect of insomnia on immune functions, focusing on the T helper 1 (Th1)/ T helper 2 (Th2) balance, by a cross-sectional design. METHODS: We provided a self-administered questionnaire to evaluate sleep habits, smoking and medical disorders to 578 men without any toxic exposure (20-64 years old), and measured natural killer (NK) cell activity in 324 men and production of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) after stimulation with phytohemagglutinin in 254 men. According to the criteria of DSM-IV, in which insomnia is classified into primary and secondary insomnia, we assessed the effect of insomnia on immune functions, controlling for age and smoking in groups with and without medical disorders. RESULTS: The prevalence of insomnia in the present study was 9.2%. In the absence of medical disorders, insomniac men had a significantly lower IFN-gamma and ratio of IFN-gamma to IL-4 than noninsomniac men. Men with insufficient sleep or difficulty initiating sleep (DIS) had a significantly lower IFN-gamma to IL-4 ratio than those not suffering from insufficient sleep or DIS. In the presence of medical disorders, insomniac men had significantly higher IL-4 than noninsomniac men. Men with difficulty maintaining sleep (DMS) had a significantly lower IFN-gamma to IL-4 ratio than men without DMS. NK cell activity was independent of insomnia. CONCLUSIONS: The present results showed a link between insomnia unrelated to medical disorders and a shift in the Th1/Th2 balance toward Th2 dominance, indicating that the relationship between sleep quality and the etiology of immune-related diseases should be reconsidered.     

Cynical hostility and stimulated Th1 and Th2 cytokine production

Hostility has been associated with heightened proinflammatory activity. However, it is not known whether greater hostility contributes to greater inflammation by promoting higher Th1 activity, lower Th2 activity, or both. The present study examines the relation of hostility to mitogen-stimulated Th1 and Th2 cytokine production in vitro. Participants were 193 healthy men and women (mean age 37.3; 44% non-white). Hostility was assessed with a 20-item version of the Cook–Medley Hostility Scale (CMHS). PHA-stimulated interleukin (IL)-2, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were used to measure Th1 activity; PHA-stimulated IL-4, IL-5, and IL-10 were used to measure Th2 activity. Greater hostility was related to greater production of two of the three Th1 cytokines, TNF-α and IFN-γ. Hostility was not associated with any measure of Th2 cytokine production. Associations with Th1 cytokines were independent of age, sex, race, socioeconomic status, body mass index, depressive symptoms, and health-related behaviors, and were consistent across men and women. Associations were not explained by social network characteristics, social support, or personality traits closely associated with social behavior. Exploratory analyses substituting the CMHS cognitive, affective, and behavioral subscales for total hostility revealed that associations between hostility and Th1 cytokine production were primarily driven by the cognitive component of hostility (i.e., cynicism). Results suggest that a unique dimension of hostility, particularly the cynicism subcomponent, that is unrelated to social factors, may influence inflammation by promoting greater Th1 cytokine production. This effect on stimulated cytokine activity may have implications for a role of hostility in exacerbating immune-related disease.     

颈动脉粥样硬化性缺血性卒中患者外周血辅助性T细胞1、2和17分布特点研究

目的探讨颈动脉粥样硬化性缺血性卒中患者外周血辅助性T细胞1、2和17(Th1、Th2和Th17)的分布特点。方法共180例颈动脉粥样硬化性缺血性卒中患者,根据颈动脉狭窄程度分为颈动脉轻度狭窄亚组、中度狭窄亚组和重度狭窄亚组(各60例),流式细胞术检测患者外周血Th1、Th2和Th17细胞比例。结果缺血性卒中组患者外周血Th1和Th17细胞比例均高于对照组[(5.76±1.81)%对(3.54±0.29)%,P=0.000;(0.36±0.13)%对(0.18±0.03)%,P=0.000]。颈动脉狭窄不同程度亚组患者外周血Th1[(4.56±0.55)%、(4.88±0.42)%和(7.83±1.69)%,P=0.000]和Th17[(0.23±0.04)%、(0.34±0.02)%和(0.50±0.09)%,P=0.000]细胞比例差异均有统计学意义,其中,重度狭窄亚组Th1(P=0.001,0.001)和Th17(P=0.000,0.001)细胞比例高于轻度狭窄亚组和中度狭窄亚组,中度狭窄亚组仅Th17细胞比例高于轻度狭窄亚组(P=0.000)。结论 Th1和Th17细胞与颈动脉粥样硬化狭窄程度密切相关,随着颈动脉狭窄程度的加重,外周血Th17细胞比例升高,表明细胞免疫机制参与颈动脉粥样硬化的发生与发展,为颈动脉粥样硬化性缺血性卒中的免疫治疗提供理论依据。     

Th1/Th2型细胞因子在实验性自身免疫性神经炎发病机制中的作用

目的 建立P2多肽诱导的实验性自身免疫性神经炎(EAN)大鼠模型,探讨Th1/Th2型细胞因子在EAN发病机制中的作用.方法 实验组用100 μg或200 μg P257-81多肽加完全弗氏佐剂(FCA)免疫Lewis大鼠,对照组单用FCA免疫,致敏后每日对大鼠进行临床评分,比较高峰期最高评分.致敏第14天测定淋巴结细胞培养液上清干扰素(IFN)-γ、IL-4及IL-10的含量,并进行坐骨神经病理学检查.结果 实验大鼠瘫痪高峰期最高评分P257-81 200 μg组(3.6±0.3)显著高于100 μg组(2.2±0.6,P＜0.01);P257-81 200 μg组大鼠病程显著长于100 μg组;IFN-γ含量,两组实验大鼠均显著高于对照组[分别为(530.6±91.7)、(806.3±132.4)和(35.0±5.9)pg/ml,均P＜0.01],而P257-81 200 μg组显著高于100 μg组(P＜0.01);IL-4和IL-10含量,P257-81 100 μg组均显著高于对照组(均P＜0.01),P257-81 200 μg组显著低于对照组(P＜0.05,P＜0.01);坐骨神经病理可见EAN急性期以炎性细胞浸润为主,P257-81 200 μg组慢性期无炎性细胞浸润,而表现为多发性局灶性脱髓鞘和神经纤维崩解未恢复.结论 EAN临床表现随致敏原P257-81多肽剂量增加而加重;在EAN急性期,IFN-γ水平与EAN临床表现大致平行;EAN疾病具有自限性可能与IL-4和IL-10水平增高有关,而疾病迁延可能与IL-4和IL-10水平降低有关.     

重症肌无力患者末梢血Th1和Th2细胞内细胞因子的变化及意义

目的研究重症肌无力(MG)患者末梢血细胞因子及抗乙酰胆碱受体抗体(AchRab)水平,探讨细胞因子在MG发病中的作用。方法研究对象为17例MG患者,分为急性期组10例,非急性期组7例,设健康对照组15例。应用流式细胞术(FCM)测定末梢血产生各型细胞因子(CK)的CD4+T细胞%,采用酶联免疫吸附法(ELISA)测定血清中抗乙酰胆碱受体抗体(AchRab)。结果⑴MG患者急性期组和非急性期组IFN-γ+IL-4-CD4+T细胞%及AchRab的含量比健康对照组显著增多(P<0.05和P<0.001);⑵急性期组和非急性期组IFN-γ-IL-4+和IL-13+CD4+T细胞%比健康对照组显著减少(P<0.05);⑶IL-10+CD4+T细胞%各组之间无显著性差异;⑷各组IFN-γ+IL-4-CD4+T细胞%与AchRab均呈正相关。结论MG患者Th1和Th2细胞因子的平衡紊乱,Th1细胞因子IFN-γ对MG患者自身抗体的产生有促进作用。     

Differential effects of Th1 and Th2 lymphocyte supernatants on human microglia

We assessed the effects of soluble molecules (supernatants) produced by pro- (Th1) and anti- (Th2) inflammatory T-cell lines on the capacity of adult human CNS-derived microglia to express or produce selected cell surface and soluble molecules that regulate immune reactivity or impact on tissue protection/repair within the CNS. Treatment of microglia with supernatants from allo-antigen and myelin basic protein-specific Th1 cell lines augmented expression of cell surface molecules MHC class II, CD80, CD86, CD40, and CD54, enhanced the functional antigen-presenting cell capacity of microglia in a mixed lymphocyte reaction, and increased cytokine/chemokine secretion (TNFalpha, IL-6, and CXCL10/IP-10). These Th1-induced effects were not reproduced by interferon-gamma (IFNgamma) alone and were only incompletely blocked by anti-IFNgamma antibody. Th2 cell supernatant treatments did not alter costimulatory/adhesion molecule expression or induce cytokine/chemokine production by microglia. Th2 treatment, furthermore, failed to reduce the induction observed in response to Th1 supernatants. Neither Th1 nor Th2 supernatants induced production of the neurotrophin molecules, nerve growth factor, or brain-derived neurotrophic factor. Our results suggest that soluble molecules released by Th1 and not Th2 cells that infiltrate the CNS can stimulate resident microglia to acquire enhanced effector and accessory cell functions; the Th1-induced effects were not downregulated by Th2 supernatant-mediated bystander suppression.     

Th1 shift in CIDP versus Th2 shift in vasculitic neuropathy in CSF

To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF, MCP-1 and MIP-1beta, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4+ T cells, IFN-gamma+ IL-4- cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-gamma/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-gamma- IL-4+ CD4+ T cell percentage, and tended to have a higher intracellular IFN-gamma/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-gamma-producing CD4+ T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.     

Melatonin modulation of lymphocyte proliferation and Th1/Th2 cytokine expression.

Melatonin is hypothesized to play a role in neuroimmunomodulation. This study investigated the in vitro effects of melatonin (10(-12) - 10(-6) M) on human peripheral blood mononuclear cell (PBMC) proliferation and T helper type 1 and T helper type 2 (Th1/Th2) cytokine expression. In vitro doses of melatonin significantly increased PBMC proliferation (p<0.05) and decreased IL-10 production in culture supernatants (p<0.05). However, there was no effect of melatonin on the stimulated production of IFN-gamma or on the intracellular accumulation of the activation antigen CD69, IFN-gamma, or IL-10 as measured by flow cytometry. These data support the notion that physiologic doses of melatonin increase lymphocyte proliferation possibly due to decreases in production of the inhibitory cytokine IL-10.     

Role of hormone-controlled Th1- and Th2-type cytokines in successful pregnancy

Development of CD4+ helper T (Th) cells into type 1 (Th1) or type 2 (Th2) effectors, as characterized by their opposite pattern of cytokine production, can be influenced by several factors, including hormones. Progesterone promotes the production of IL-4 and IL-5, whereas relaxin promotes the production of IFN-gamma by T cells. Leukemia inhibitory factor (LIF), essential for embryo implantation, is up-regulated by IL-4 and progesterone. Moreover, the production of LIF and/or Th2 cytokines by decidual T cells contributes to the maintenance of pregnancy. Our results suggest that relaxin and progesterone may contribute to the regulation of the immune homeostasis during pregnancy.     

从Th1、Th17细胞除极探讨丙戊酸干预实验性自身免疫性神经炎的机制

目的从Ⅰ型辅助T细胞(Th1)、17型辅助T细胞(Th17)细胞除极角度探讨丙戊酸(VPA)干预实验性自身免疫性神经炎(EAN)的机制。方法实验大鼠随机分为VPA治疗组、EAN组、正常组,应用周围神经髓鞘抗原(P257-81)多肽与完全弗氏佐剂的混合液免疫VPA治疗组和EAN组大鼠。VPA治疗组大鼠于免疫当天至第15天每天腹腔内注射300mg·kg-1丙戊酸钠。观察发病情况,坐骨神经电生理改变及组织病理学变化,检测腹股沟淋巴结中IFN-γ、IL-17 mRNA水平。结果 VPA治疗组的最初发病时间迟于EAN组(P<0.05),其高峰期临床评分显著低于EAN组(P<0.05),坐骨神经复合肌肉动作电位(CMAP)的波幅较EAN组明显升高,潜伏期和时限显著缩短(P<0.05)。髓鞘脱失和炎性细胞浸润较EAN组明显减少(P<0.05)。淋巴结中IFN-γ、IL-17mRNA表达明显下降(P<0.05)。结论 VPA通过影响Th1、Th17细胞除极,使IFN-γ、IL-17分泌下降,从而抑制EAN大鼠的自身免疫反应。     

Atorvastatin-modified dendritic cells in vitro ameliorate experimental autoimmune myasthenia gravis by up-regulated Treg cells and shifted Th1/Th17 to Th2 cytokines

Conventional therapies for autoimmune diseases produce nonspecific immune suppression, which are usually continued lifelong to maintain disease control, and associated with a variety of adverse effects. In this study, we found that spleen-derived dendritic cells (DCs) from the ongoing experimental autoimmune myasthenia gravis (EAMG) rats can be induced into tolerogenic DCs by atorvastatin in vitro. Administration of these tolerogenic DCs to EAMG rats on days 5 and 13 post immunization (p.i.) resulted in improved clinical symptoms, which were associated with increased numbers of CD4⁺CD25⁺ T regulatory (Treg) cells and Foxp3 expression, decreased lymphocyte proliferation among lymph node mononuclear cells (MNC), shifted cytokine profile from Th1/Th17 to Th2 type cytokines, decreased level of anti-R97–116 peptide (region 97–116 of the rat acetylcholine receptor α subunit) IgG antibody in serum. These tolerogenic DCs can migrate to spleen, thymus, popliteal and inguinal lymph nodes after they were injected into the EAMG rats intraperitoneally. Furthermore, these tolerogenic DCs played their immunomodulatory effects in vivo mainly by decreased expression of CD86 and MHC class II on endogenous DCs. All these data provided us a new strategy to treat EAMG and even human myasthenia gravis (MG).     

Th1/Th2免疫应答系统在冠状动脉支架内再狭窄患者中的表达*☆

背景：支架再狭窄的机制尚未阐明,炎症失衡在多种疾病中起重要做用,可能与支架再狭窄有关。 目的：观察冠状动脉支架置入后支架内再狭窄患者辅助T细胞亚型Th1样细胞因子γ-干扰素、白细胞介素2和Th2样细胞因子白细胞介素4、白细胞介素10在血清中的分布特点。 方法：应用酶联免疫吸附法测定32例冠状动脉内支架置入后合并支架内再狭窄患者血清标本中γ-干扰素、白细胞介素2、白细胞介素4、白细胞介素10的浓度(实验2组),并与未行支架置入但排除冠心病患者30例(对照1组)、未行支架置入的冠心病患者30例(对照2组)及行支架置入但是无支架内狭窄患者30例(实验1组)进行比较。 结果与结论：对照2组血清中γ-干扰素、白细胞介素2、白细胞介素4、白细胞介素10的水平与对照1组相比,差异无显著性意义(P > 0.05);实验1组各指标与对照1组相比,差异亦无显著性意义(P > 0.05);实验2组患者血清中γ-干扰素、白细胞介素2水平高于其他3组(P < 0.01);白细胞介素4、白细胞介素10水平则低于对照1组和实验1组(P < 0.01)。结果表明支架内再狭窄患者存在Th1、Th2炎症水平的失衡,Th1型细胞因子上调,Th2型细胞因子下调,提示Th1/Th2失衡可能是冠状动脉支架内再狭窄的重要原因。 关键词：支架;冠心病;T淋巴细胞;辅助诱导;干扰素Ⅱ型;白细胞介素     

Regulation of Th1 and Th2 lymphocyte migration by human adult brain endothelial cells.

Endothelial cells of the blood-brain barrier (BBB) have the ability to regulate and restrict the passage of cells and molecules from the periphery to the CNS. We have used an in vitro assay of lymphocyte migration across monolayers of human adult brain endothelial cells (HBEC) as a model of lymphocyte migration across the BBB. We found that human allogeneic or MBP-reactive Th2-polarized lymphocytes migrate more avidly than Th1-polarized lymphocytes. Migration of Th2 but not Th1 cells across brain endothelium was inhibited by antibodies directed at MCP-1, a chemokine produced by HBECs. We could detect CCR2, a chemokine receptor that recognizes MCP-1 on Th2 but not Th1 lymphocytes. ICAM-1 and VCAM-1 molecules were expressed on the surface of HBECs under basal conditions and were upregulated by Th1 but not Th2 cell-derived supernatants. Migration of both lymphocyte subsets was dependent on LFA-1/ICAM-1 interactions. Blocking VLA-4/VCAM-1 binding did not influence actual trans-endothelial migration. These results suggest that HBECs composing the BBB favor the migration of Th2 cells. We postulate that this selectivity may help prevent activated Th1 lymphocytes, the putative CNS autoimmune disease initiating cells, from reaching the CNS parenchyma and favor entry of Th2 cells, a putative means to induce bystander suppression in the CNS.     

Reciprocal Th1 and Th17 regulation by mesenchymal stem cells: Implication for multiple sclerosis

Human mesenchymal stem cells (hMSCs) are being considered for clinical trials of multiple sclerosis (MS). We examined the effects of adult bone marrow‐derived hMSCs on responses of primary human Th1, Th17, and Th1/17 double‐expressing T‐cell subsets, all implicated in MS. As expected, soluble products from hMSCs inhibited Th1 responses; however, Th17 responses were increased. Secretion of interleukin (IL)‐10, considered anti‐inflammatory, was decreased. Pretreating hMSCs with the proinflammatory cytokine IL‐1β accentuated these effects, and caused decreases in the Th1/17 subset. These findings underscore the importance of further preclinical work and immune‐monitoring to define hMSC effects on disease‐relevant immune responses under variable conditions. ANN NEUROL 2010