IL-12对BALB/c小鼠Th17细胞的分化的影响

目的: 观察细胞因子IL-12对Th17细胞分化的影响.方法: 小鼠脾淋巴细胞经抗CD3单克隆抗体(mAb)和不同浓度的重组小鼠IL-12刺激, 3 d后使用ELISA方法观察培养物上清液中IL-17的产生情况.并使用细胞内细胞因子染色的方法, 通过流式细胞术观察CD3 mAb和重组小鼠IL-12刺激对Th1和Th17细胞分化的影响.结果: Th17细胞不分泌IFN-γ、 IL-5、 IL-10等细胞因子, 不表达Foxp3, 是一个独立的细胞亚群.不同浓度的重组小鼠IL-12可以诱导抗CD3 mAb 的T细胞分泌IFN-γ, 并向Th1细胞方向分化.同时, IL-12可以抑制活化的T细胞分泌IL-17, 抑制T细胞向Th17细胞分化.结论: IL-12可以抑制Th17细胞的分化.     

灵芝多糖通过上调STAT4促进人外周血淋巴细胞中Th1细胞的分化

目的 探讨灵芝多糖(GLP)对外周血淋巴细胞免疫分群的影响及其作用机制.方法 取肿瘤患者和正常人的外周血,分离外周血单个核细胞(PBMC)后,用不同剂量的GLP(10 ng/ml、50ng/ml和100 ng/ml)刺激后,用流式细胞仪检测DC细胞表面分子(HLA-DR、CD83和CD11c)、Th1细胞、Th2细胞和NK(CD3-CD56+)细胞数;并进一步用免疫磁珠分选出正常人外周血CD4+ Th细胞后用不同浓度GLP刺激24h后,荧光实时定量Q-PCR检测Th1和Th2细胞因子的表达水平,Westernblot分析Th1分化相关的转录因子水平.结果 灵芝多糖可以在体外呈浓度依赖性增加外周血中Th1细胞亚群和DC共刺激分子的表达(P＜0.01),并且增加STAT4的表达和IL-12、IFN-γ和TNF-α的mRNA的表达水平(P＜0.01).结论 灵芝多糖可能通过增加Th细胞STAT4的表达水平,促进其向Th1细胞分化,并增加Th1的分泌细胞因子.     

雷公藤对IL2的产生和IL2受体表达的抑制作用

观察雷公藤对T淋巴细胞免疫应答的抑制作用,发现雷公藤水煎液抑制小鼠脾细胞和胸腺细胞用ConA诱导的增殖反应,抑制作用与雷公藤剂量呈正比例。5mg/ml雷公藤完全抑制脾细胞的ConA增殖反应;该剂量雷公藤与脾细胞共育2小时不影响脾细胞的活率,细胞经洗涤后对CouA的增殖反应与正常细胞相同。进一步研究,在ConA诱导脾细胞72小时培养的早期加入雷公藤,完全抑制细胞的增殖反应;而在培养后期加入仅见部份抑制作用,推测雷公藤是抑制细胞的活化而不是对细胞的直接毒性作用和对DNA合成的抑制。ConA诱导脾细胞表达IL2受体和分泌IL2。雷公藤的加入完全抑制受体的表达,也抑制但不完全抑制细胞分泌IL2。外源性IL2的加入也不能逆转雷公藤对脾细胞ConA增殖反应的抑制作用,提示IL2分泌的减少与细胞DNA合成的抑制无直接联系。此外,IL2受体表达的受阻与DNA合成受抑制之间的联系还有待深入研究。     

大肠杆菌麦芽糖结合蛋白（MBP）诱导小鼠Th1细胞的活化作用

目的:探讨MBP对小鼠T细胞的调节作用.方法:采用淋巴细胞分层液分离小鼠脾脏淋巴细胞,在体外用MBP刺激淋巴细胞,通过MTT法测定淋巴细胞增殖反应;ELISA检测脾细胞培养上清中细胞因子的分泌水平;MBP免疫小鼠后,ELSPOT检测MBP刺激脾淋巴细胞分泌IFN-γ的细胞频数;免疫组化检测MBP与T细胞的结合作用.结果:MBP以剂量依赖关系促进小鼠淋巴细胞的增殖,促进淋巴细胞分泌IL-2和IFN-γ,轻微抑制IL-4的分泌;ELSPOT检测细胞分泌IFN-γ结果显示,MBP可诱导特异性Th1活化,也可刺激非特异性Th1活化;免疫组化结果显示,抗MBP抗体可与经MBP刺激的淋巴细胞发生反应,阳性细胞占总淋巴细胞的37.7%,当MBP采用 1∶2 000抗MBP抗体中和后,再与淋巴细胞反应,结果未见阳性细胞.结论:MBP可作用于淋巴细胞诱导非特异性Th1活化,也可通过免疫诱导大量特异性Th1活化;MBP可作为新的免疫增强剂开发利用.     

淫羊藿甙对小鼠T淋巴细胞体外中期和晚期活化的影响

目的:研究淫羊藿甙(ICA)对刀豆蛋白A(ConA)刺激的小鼠T淋巴细胞体外中期和晚期活化的影响.方法:采用流式细胞术(FCM)结合双色荧光抗体染色技术分别检测中期和晚期活化标志CD25和CD71分子的表达; 取中期活化的细胞上清, 利用LuminexTM100分析上清中IL-2、 IL- 4、 IL-10、 TNF-α、 IFN-γ的含量变化.结果:ICA在终浓度0.3、 1.5、 3.0 μmol/L时明显抑制CD25的表达而对CD71没有明显影响; 下调Th2型细胞因子及上调Th1型细胞因子的分泌量, 但没有剂量依赖效应.结论:ICA下调CD25、 IL-2和Th2型细胞因子水平, 抑制T细胞活化, 同时有一定程度的促进细胞免疫反应, 因此ICA可能具有双向调节免疫平衡的作用.     

T淋巴细胞内三磷酸肌醇传递ConA诱导的增殖信号

本文研究了不同浓度ConA诱导的人外周血T淋巴细胞内1-磷酸肌醇(IP_1),2-磷酸肌醇(IP_2),3-磷酸肌醇(IP_3)的变化。结果显示,不同剂量ConA刺激早期,细胞内IP_3、IP_2及IP_1水平均有所增高,尤以IP_3水平增高最为显著,与对照组比较增加率为107％,但各剂量组间无差异。PHA慢性处理后IL—2R表达阳性的T细胞,ConA不引起IP_3及相关产物的变化,但用抗IL-2R的单克隆抗体(抗Tac McAb)封闭T细胞的IL—2R后,ConA刺激可使细胞内IP_3水平明显增加。这提示:IP_3可能作为第二信使介导了ConA诱导的细胞增殖分化,但IL-2R表达可抑制丝裂原信息经IP_3途径传递,这种抑制作用可为抗Tac McAb所消除。     

泡球蚴感染小鼠中Tim-3 对Th1 / Th2 细胞因子平衡的影响作用研究

目的:研究泡球蚴感染小鼠Tim-3、Th1细胞因子γ干扰素(IFN-γ)、Th2细胞因子白细胞介素4(IL-4)的变化。方法:建立泡球蚴感染小鼠模型和对照组,取小鼠脾脏,分离脾淋巴细胞,流式细胞技术检测脾淋巴细胞Th1和Th2细胞水平以及Tim-3在Th1和Th2上的表达水平,用流式微珠阵列技术(CBA)法检测小鼠外周血清中IFN-γ、IL-4水平。结果:与正常对照组相比,泡球蚴感染小鼠脾淋巴细胞Tim-3在Th1中表达增高,Tim-3+Th1细胞与IFN-γ水平呈负相关。结论:泡球蚴诱导小鼠Tim-3在Th1细胞高表达,下调Th1免疫应答介导了Th1/Th2失衡。     

丹皮酚通过STAT3通路抑制IL-17A诱导的角质形成细胞活性和细胞因子分泌

目的:观察丹皮酚对白细胞介素17A(IL-17A)诱导的人角质形成细胞活性、细胞因子分泌及相关信号转导通路的影响。方法:采用IL-17A(200μg/L)刺激体外培养的HaCaT细胞,同时加入不同浓度(200 mg/L和100 mg/L)丹皮酚共同培养24 h。采用CCK-8法测定细胞的活力;CBA法测定Th1/Th2/Th17类炎症细胞因子的变化;ELISA法测定炎症细胞因子IL-23的水平;real-time PCR法测定炎症因子IL-23、IL-6、CXCL2、CXCL8、CCL20和STAT3的mRNA表达;Western blot法测定信号转导通路中STAT3和ERK1/2的蛋白水平。结果:丹皮酚能够显著抑制IL-17A诱导的HaCaT细胞的活力(P0.05);丹皮酚能够减少IL-6的分泌,同时,能够降低IL-23、CXCL2、CXCL8和CCL20的mRNA表达,并对细胞内STAT3的mRNA和蛋白表达有一定的抑制作用,而对ERK1/2的蛋白水平无显著影响。结论:丹皮酚能够抑制IL-17A诱导的HaCaT细胞的活性和细胞因子的分泌,其作用机制可能与STAT3通路有关。     

环孢素A对小鼠Th17细胞分化的影响

目的：观察在抗CD3单克隆抗体（mAb）＋rIL-23刺激的条件下，环孢素A（CsA）对Th17细胞分化的影响。方法：小鼠脾淋巴细胞分别使用抗CD3mAb、抗CD3mAb＋rIL-23及抗CD3mAb＋rIL-23＋不同浓度的CsA刺激后，用ELISA检测IL-17和IFN-7的水平，并用流式细胞仪在单个细胞水平上检测产生IL-17的T细胞亚群。结果：单独抗CD3mAb能诱导少量的IL-17产生，加入IL-23后呈剂量依赖的方式明显增加IL-17的产生。CsA对抗CD3mAb＋rIL-23诱导的Th17细胞分化呈剂量依赖性的抑制作用。CsA不仅抑制早期Th17的分化，当细胞激活48小时后，CsA对Th17细胞的分化仍有抑制作用。CsA除了抑制Th17细胞分化外，对IFN-7和IL-2的产生也有抑制作用。此外，T细胞亚群分析的结果表明IL-17主要由CD4＋T细胞产生，而CD8＋T细胞几乎不产生IL-17。结论：CsA可以抑制Th17细胞的分化，进一步阐明了CsA免疫抑制及抗炎作用的机制，为临床上应用CsA提供科学理论和实验依据。     

褐藻多糖硫酸酯体外诱导树突状细胞成熟

目的探讨清道夫受体A(SR-A)非脂蛋白配体,褐藻多糖硫酸酯(Fucoidan),对人体外培养的单核诱导的树突状细胞(monocyte derived DC,MDDC)的影响及其机制。方法采用免疫磁珠法,直接分离外周血单核细胞并通过GM-CSF,IL-4诱导生成MDDC,经Fucoidan或LPS刺激后,用流式细胞技术(FCM)检测树突状细胞表面协同刺激分子表达及细胞吞噬能力的变化;酶联免疫吸附法(ELISA)检测MDDC及Th细胞分泌的细胞因子;CFSE法检测经刺激后MDDC对Th细胞活化、增殖的影响。结果经流式细胞分析术检测,Fucoidan刺激后的MDDC膜表面CD80、CD83及MHC-Ⅱ分子的表达均增强,其中CD83分子表达上调呈剂量依赖性,同时MDDC吞噬能力减弱;IL-10,IL-12p40和TNF-α的分泌增加;并且可以诱导Th细胞的分泌IFN-γ并诱导其增殖。结论 Fucoidan在体外可以诱导MDDC的成熟、活化,刺激其分泌相关细胞因子,发挥其免疫应答中抗原呈递,促进Th活化、增殖分化的作用;通过该作用阐明Fucoidan及SR-A在DC的活化和成熟过程中的作用。     

过表达IL-17RLM的人脐带间充质干细胞对TNBS诱导的结肠炎小鼠脾脏淋巴细胞的免疫调节作用

目的:研究过表达白细胞介素17受体样分子的人脐带间充质干细胞(IL-17RLM-hUCMSCs)对三硝基苯磺酸(TNBS)诱导的结肠炎小鼠脾脏淋巴细胞的免疫调节作用,为炎症性肠病的干细胞治疗提供优化的种子细胞。方法:体外分离培养hUCMSCs,利用慢病毒载体向干细胞内转入IL-17RLM基因,构建IL-17RLM-hUCMSCs。采用TNBS诱导小鼠实验性结肠炎模型,无菌取炎症小鼠脾脏制备淋巴细胞悬液,在刀豆蛋白A(Con A)刺激下将淋巴细胞分别与不同浓度的IL-17RLM-hUCMSCs及hUCMSCs共培养,72 h后以淋巴细胞+Con A为阳性对照,CCK8法及CFSE标记法检测淋巴细胞的增殖情况;同时用流式细胞术检测T淋巴细胞亚群(Th1、Th2、Th17及Treg)比例的改变。结果:hUCMSCs及IL-17RLM-hUCMSCs均对ConA刺激下的淋巴细胞增殖有抑制作用(P0.05);当MSCs/淋巴细胞为1∶1~1∶10时,MSCs对淋巴细胞增殖的抑制作用呈现浓度依赖性。在有效浓度范围内,IL-17RLM-hUCMSCs较h UCMSCs抑制作用更强(P0.05)。hUCMSCs及IL-17RLM-h UCMSCs均能够下调结肠炎小鼠脾脏淋巴细胞的Th1和Th17细胞亚群比例,上调Treg细胞亚群比例,但IL-17RLM-h UCMSCs对Th17细胞亚群的抑制作用更显著(P0.05)。结论:IL-17RLM-hUCMSCs呈浓度依赖性地抑制TNBS诱导的结肠炎小鼠脾脏淋巴细胞增殖,且该作用优于h UCMSCs。同时,IL-17RLM-hUCMSCs可调节T细胞亚群的免疫平衡,且抑制Th17细胞亚群作用强于hUCMSCs。     

乳杆菌对原代淋巴细胞中Th1/Th2细胞平衡的影响

目的:分析7种乳杆菌对原代淋巴细胞增殖和细胞因子(CK)分泌的作用,进而探讨其对Th1/Th2细胞平衡的影响。方法:用不同种属、不同浓度的活的/热致死的乳杆菌体外作用于小鼠脾淋巴细胞培养60 h后,采用MTT比色法检测淋巴细胞的增殖效果。用ELISA法检测Th1型细胞因子(IL-12、IFN-γ)、Th2型细胞因子(IL-4、IL-10)和调节型细胞因子(TGF-β)的分泌量。结果:活的/热致死的乳杆菌单独作用,就能促进淋巴细胞体外增殖并表现出剂量依赖关系(P<0.05)。当菌的浓度为107集落形成单位(CFU)/mL(即细菌与细胞的比例为10∶1)时,热致死的发酵乳杆菌和嗜酸乳杆菌的免疫活性近似于活菌。而且,这两株热致死菌还可适当提高淋巴细胞分泌IL-12和IFN-γ,抑制IL-4、IL-10和TGF-β的分泌,使其IFN-γ/IL-4的比值(代表Th1/Th2细胞平衡)均显著高于刀豆蛋白A(ConA)对照组(P<0.05)。结论:乳杆菌可通过提高淋巴细胞的IFN-γ/IL-4分泌率来促进Th1优势状态的Th1/Th2细胞平衡,并具有菌株特异性。     

Splenic T-lymphocyte functions during early syphilitic infection are complex.

Immune regulation during syphilitic infection is extremely complex. This paper presents findings on the early events of T-cell activation following testicular infection in rabbits. Treponema pallidum was preincubated for 24 h with nonadherent spleen cells. After being washed to remove the organisms, these spleen cells were either stimulated with concanavalin A (ConA) to induce interleukin-2 (IL-2), or added to adherent cells that were then stimulated with lipopolysaccharide to induce IL-1. Preincubation with the treponemes up-regulated nonadherent cell functions. These sensitized cells increased their IL-2 production and augmented macrophage IL-1 synthesis. In sharp contrast, if this preincubation step was omitted, down-regulation was apparent. When T. pallidum was directly incubated with nonadherent cells in the presence of ConA, reduced levels of IL-2 were detected. Nonadherent cells from infected rabbits secreted soluble suppressive factors after 48 h of in vitro incubation; these factors inhibited ConA-induced IL-2 generation as well as ConA-induced lymphocyte proliferation. At least some of this suppressive activity was attributed to transforming growth factor. In addition, when T lymphocytes were depleted, less suppression was detected. Treponemes also inhibited ConA-induced T-cell proliferation, and monophosphoryl lipid A reversed this inhibitory effect. Since monophosphoryl lipid A neutralizes T-suppressor activity, these findings further suggest a role for T-suppressor activity during syphilitic infection. Finally, T. pallidum directly stimulated IL-2 synthesis when coincubated with phorbol myristate acetate. This agent reverses the prostaglandin E2 blockage of T-helper cell protein kinase C, a necessary second messenger signal for IL-2 synthesis. In summary, T-cell functions are extremely complex and represent a composite of both stimulation and down-regulation, which occur concurrently but to different degrees.     

Effects of boar seminal immunosuppressive fraction on production of cytokines by Concanavalin A-stimulated spleen cells and on proliferation of B lymphoma cell lines

PROBLEM: The immunosuppressive fraction (ISF) of boar seminal vesicle fluid has recently been demonstrated to inhibit mitogen-stimulated proliferation of lymphocytes and antibody response to corpuscular and soluble antigens. The effects of ISF on in vitro and in vivo production of cytokines as well as its possible inhibitory effect on proliferation of B lymphoma cells remain to be elucidated. METHODS: The effect of ISF on proliferation of normal mouse spleen cells stimulated by Concanavalin A (Con A) and on mouse B lymphoma cells was measured by 3H-thymidine incorporation. Cytokines were determined in the supernatants of mouse spleen cells stimulated with Con A in the presence or absence of ISF by enzyme-linked immunosorbent assay (ELISA). In vivo cytokine production in the sera samples of mice treated with ISF and immunized with keyhole limpet hemocyanin (KLH) was followed by ELISA, too. RESULTS: We confirmed the inhibitory effect of ISF on Con A-stimulated lymphocyte proliferation. ISF affected cytokine production in the Con A-stimulated spleen cells: production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) was lowered, but production of IL-4, IL-6, and IL-10 was enhanced. Similarly, in the sera samples of mice immunized with keyhole limpet hemocyanin (KLH), IL-2 and IFN-gamma levels were decreased by ISF. ISF inhibited proliferation of Ag 8 and X 63-IL-2 B lymphoma cells as well. CONCLUSIONS: ISF inhibited production of T helper1 (Th1) cytokines (IL-2 and IFN-gamma) and enhanced production of Th2 cytokines (IL-4, IL-6, and IL-10). ISF seems to shift the Th1/Th2 pattern in favor of Th2. ISF exhibited an antiproliferative activity on mouse B lymphoma cells.     

Study of the NKT cell subsets with superantigen SEB-activated tolerance

AIM: To study the NKT cell subsets and their differentiation. METHODS: Splenic lymphocytes from C57BL/J mice that had received SEB treatment were collected as effector cells on the 10(th) day. The cells were cultured in medium containing ConA, LPS and IL-2 for 3 days and measured their response to mitogens and cytokine. The inhibitory action of the effector cells was examined. The effector cells were cultured with normal lymphocytes and above mitogens or cytokine for 3 day. The cells proliferation was assessed with MTT method.The NKT cell subsets among these effector cells with the tolerance function were analyzed and their differentiation sources and correlation of functions were detected by flow cytometry. RESULTS: The response of SEB-activated effector cells to ConA, LPS and IL-2 was significantly decreased compared with that of normal lymphocytes. The A values of cell proliferation were decreased from 0.80+/-0.04, 0.60+/-0.03 and 0.55+/-0.07 in control groups to 0.60+/-0.05, 0.30+/-0.05 and 0.27+/-0.04 in effector groups, respectively (P<0.01, n=3).The inhibitory ability of effectors cells against the response of normal lymphocytes to ConA, LPS and IL-2 were clearly observed. They inhibited the response of normal lymphocytes to several mitogens and cytokine. And the A values of cell proliferation were decreased to 0.26+/-0.02, 0.48+/-0.04 and 0.34+/-0.02, respectively (P<0.01, n=3). The CD4(+)NK1.1(+), CD8(+)NK1.1(+), TcRV8(+)NK1.1(+) NKT cell subsets among SEB-activated effector cells with tolerance function were significantly increased and shown that they come from T cell population. And the CD4(-)CD8(-)/NK1.1(+)CD3(+)NKT cells by ConA or SEB-activated were shown coming from NK cell population. CONCLUSION: The effector cells with tolerance function activated by superantigen SEB relate to CD4(+)NK1.1(+), CD8(+)NK1.1(+), TcRVbeta8(+)NK1.1(+) NKT cell subsets. The NKT cell subsets come from T cells. The CD4(-)CD8(-)/NK1.1(+)CD3(+)NKT cells differentiating from NK cells are not involved in the regulation of tolerance.     

The effects of dehydroepiandrosterone (DHEA) on in vitro spleen cell proliferation and cytokine production.

Dehydroepiandrosterone (DHEA), a weak androgenic steroid, has been associated with enhancing immune responses and upregulating resistance against viral, parasitic, and bacterial infections. The objective of this study was to assess the effects of DHEA on murine spleen cell viability, proliferation, and cytokine production following in vitro stimulation with the mitogens concanavalin A (ConA) and lipopolysaccharide (LPS). Results showed that exposure to 6 microM DHEA significantly decreased the viability and proliferation of murine spleen cells stimulated with LPS, whereas no effect was seen on murine spleen cells stimulated with ConA. DHEA did influence the production of both ConA-induced and LPS-induced cytokines. DHEA also significantly reduced the mitogen-induced production of the proinflammatory cytokine interleukin-1 (IL-1) as well as the Th1 cytokines IL-2 and interferon-gamma (IFN-gamma). Increasing concentrations of DHEA significantly increased the production of the Th2 cytokine IL-10 but had no effect on the production of the Th2 cytokine IL-4, the proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), or IL-6. These results suggest that DHEA may be an important factor for increasing Th2 cytokine production and decreasing Th1 and proinflammatory cytokine production. This study provides a more comprehensive understanding of the effects of DHEA on the rates of cell proliferation, cell viability, and cytokine production.     

HMGB1对淋巴细胞增殖、凋亡及Th1/Th2、Tc1/Tc2漂移的影响

目的:探索HMGB1是否参与淋巴细胞免疫功能的调节.方法:系列浓度HMGB1单独或与ConA联合刺激培养小鼠脾淋巴细胞.MTT法检测细胞增殖,流式细胞术(FCM)检测细胞凋亡、细胞表面CD3、CD8及细胞内IL-4、IFN-γ表达.结果:(1)HMGB1时间-剂量依赖性调节淋巴细胞增殖,而不影响其凋亡.(2)不同HMGB1浓度和刺激时间不影响淋巴细胞Th1、Th2及Th1/Th2变化,但10 μg/L和100 μg/L HMGB1刺激12～24 h,Th1亚群占优势;培养12～24 h,淋巴细胞Tc1亚群明显减少,Tc2无变化.Tc1/Tc2变化显示,1 μg/L和10 μg/L HMGB1刺激,Tc1亚群占优势.(3)培养12～24 h,上清中IL-2增加,sIL-2R减少,IL-2/sIL-2R比例升高20～50倍,尤以10 μg/L HMGB1刺激明显.结论:低剂量HMGB1可增强淋巴细胞免疫功能.     

Regulation of murine interleukin-10 production by dehydroepiandrosterone.

Dehydroepiandrosterone (DHEA), one of the predominant androgens secreted by the adrenal cortex, is a potential immunologic regulator. In this report, the effect of DHEA on interleukin-10 (IL-10) production was studied in vivo. Mice were injected s.c. with DHEA or DHEA-sulfate (DHEAS) ranging from 50 microg to 500 microg/g body weight. The serum was collected, and the spleen cells were isolated 48 h after treatment. Results indicate that treatment with DHEA or DHEAS significantly increases the serum level of IL-10. The spleen cells isolated from the DHEA-treated or DHEAS-treated mice also showed an increase in IL-10 secretion and mRNA expression after the cells were activated by concanavalin A (ConA). The maximal dose of DHEA for inducing IL-10 production was 250 microg/g body weight. As IL-10 is a potent differentiation factor of B lymphocytes, the possible role of DHEA in regulation of immunoglobulin (Ig) production was studied in vivo. Results indicated a significant increase in both serum level of Ig (IgG, IgM, IgA) and Ig secretion by spleen cells after the mice were treated with DHEA or DHEAS. Mice injected with both DHEA (250 microg/g body weight) and anti-IL-10 antibody (0.5 mg/g body weight) showed a significantly reduced DHEA-mediated increase in Ig production. Thus, DHEA might affect the function of B lymphocytes via stimulating IL-10 production.     

Dietary fatty acids influence the production of Th1- but not Th2-type cytokines

C57B16 mice were fed for 6 weeks on a low-fat diet or on high-fat diets containing coconut oil (rich in saturated fatty acids), safflower oil [rich in n-6 polyunsaturated fatty acids (PUFAs)], or fish oil (rich in n-3 PUFAs) as the main fat sources. The fatty acid composition of the spleen lymphocytes was influenced by that of the diet fed. Thymidine incorporation into concanavalin A-stimulated spleen lymphocytes and interleukin (IL)-2 production were highest after feeding the coconut oil diet. Interferon (IFN)-gamma production was decreased by safflower oil or fish oil feeding. IL-4 production was not significantly affected by diet, although production was lowest by lymphocytes from fish oil-fed mice. The ratio of production of Th1- to Th2-type cytokines (determined as the IFN-gamma/IL-4 ratio) was lower for lymphocytes from mice fed the safflower oil or fish oil diets. After 4 h of culture, IL-2 mRNA levels were higher in cells from mice fed coconut oil, and IFN-gamma mRNA levels were higher in cells from mice fed coconut oil or safflower oil. After 8 h of culture, IL-2, IFN-gamma, and IL-4 mRNA levels were lowest in cells from mice fed fish oil. The ratio of the relative levels of IFN-gamma mRNA to IL-4 mRNA was highest in cells from mice fed coconut oil and was lowest in cells of mice fed fish oil. The influence of individual fatty acids on IL-2 production by murine spleen lymphocytes was examined in vitro. Although all fatty acids decreased IL-2 production in a concentration-dependent manner, saturated fatty acids were the least potent and n-3 PUFAs the most potent inhibitors, with n-6 PUFAs falling in between in terms of potency. It is concluded that saturated fatty acids have minimal effects on cytokine production. In contrast, PUFAs act to inhibit production of Th1-type cytokines with little effect on Th2-type cytokines; n-3 PUFAs are particularly potent. The effects of fatty acids on cytokine production appear to be exerted at the level of gene expression.     

Immunoregulatory roles of interleukin-13 in cattle.

Interleukin-13 (IL-13) is produced predominantly by helper T lymphocytes of the Th2 phenotype and mediates its effects on several immune cells, including B lymphocytes and macrophages, stimulating their proliferation, differentiation, and effector functions. IL-13 activates human B cells but has no detectable activity on murine B lymphocytes, suggesting that the activity of IL-13 varies among species. Our studies show that IL-13 enhances proliferation and differentiation of bovine B cells and upregulates cell surface major histocompatibility complex (MHC) class II expression. We examined mRNA expression of the putative signaling component of the bovine IL-13Ralpha1 homolog in several peripheral blood populations. After stimulation with calcium ionophore and phorbol ester, IL-13Ralpha1 mRNA levels appeared to be downmodulated in T cells, upregulated in macrophages and B cells, and unchanged in neutrophils. Together, these studies begin to provide insight into the relative importance of IL-13 in immunoregulation in cattle.