Reduced IL-2 expression in NOD mice leads to a temporal increase in CD62Llo FoxP3+ CD4+ T cells with limited suppressor activity

IL-2 plays a critical role in the induction and maintenance of FoxP3-expressing regulatory T cells (FoxP3(+) Tregs). Reduced expression of IL-2 is linked to T-cell-mediated autoimmune diseases such as type 1 diabetes (T1D), in which an imbalance between FoxP3(+) Tregs and pathogenic T effectors exists. We investigated the contribution of IL-2 to dysregulation of FoxP3(+) Tregs by comparing wildtype NOD mice with animals congenic for a C57BL/6-derived disease-resistant Il2 allele and in which T-cell secretion of IL-2 is increased (NOD.B6Idd3). Although NOD mice exhibited a progressive decline in the frequency of CD62L(hi) FoxP3(+) Tregs due to an increase in CD62L(lo) FoxP3(+) Tregs, CD62L(hi) FoxP3(+) Tregs were maintained in the pancreatic lymph nodes and islets of NOD.B6Idd3 mice. Notably, the frequency of proliferating CD62L(hi) FoxP3(+) Tregs was elevated in the islets of NOD.B6Idd3 versus NOD mice. Increasing levels of IL-2 in vivo also resulted in larger numbers of CD62L(hi) FoxP3(+) Tregs in NOD mice. These results demonstrate that IL-2 influences the suppressor activity of the FoxP3(+) Tregs pool by regulating the balance between CD62L(lo) and CD62L(hi) FoxP3(+) Tregs. In NOD mice, reduced IL-2 expression leads to an increase in nonsuppressive CD62L(lo) FoxP3(+) Tregs, which in turn correlates with a pool of CD62L(hi) FoxP3(+) Tregs with limited proliferation.     

Regulatory T cells in viral hepatitis

The pathogenesis and outcome of viral infections are significantly influenced by the host immune response. The immune system is able to eliminate many viruses in the acute phase of infection. However, some viruses, like hepatitis C virus (HCV) and hepatitis B virus (HBV), can evade the host immune responses and establish a persistent infection. HCV and HBV persistence is caused by various mechanisms, like subversion of innate immune responses by viral factors, the emergence of T cell escape mutations, or T cell dysfunction and suppression. Recently, it has become evident that regulatory T cells may contribute to the pathogenesis and outcome of viral infections by suppressing antiviral immune responses. Indeed, the control of HCV and HBV specific immune responses mediated by regulatory T cells may be one mechanism that favors viral persistence, but it may also prevent the host from overwhelming T cell activity and liver damage. This review will focus on the role of regulatory T cells in viral hepatitis.     

1,25-二羟维生素D3的免疫调节机理及其应用进展

1,25-二羟维生素D3[1,25（OH）2D3]不仅具有调节钙磷代谢的作用,还可影响多种细胞的生长和分化,具有调节免疫系统的作用.该文综述1,25（OH）2D3的免疫调节机制,为进一步开发更安全有效的类似物,并作为新兴的免疫调节剂应用于临床提供理论依据.     

Ig-binding Receptors on Human NK Cells as Effector and Regulatory Surface Molecules

The receptors on human natural killer 9NK cells which can specifically bind the Fc portion of immunoglobulin molecules (Fc receptors) have been extensively studied. The best known and studied Fc receptor on human NK cells is FcγRIIIa. Interactions of NK cells with IgG antibodies via this receptor are well known to induce a signal transduction cascade and lead to antibody-dependent cell-mediated cytotoxicity (ADCC) as well as release of various cytokines. In addition, interactions with monomeric IgG and FcγRIIIa have been demonstrated, which result in negative regulation of NK activity and other immunomodulatory effects. Over the past several years, it has also become increasingly appreciated that human NK cells express a variety of other Fc receptors, including FcμR, which also can mediate effector and immunoregulatory functions. Also, a novel form of FcγR has been demonstrated on human NK cells, termed FcγRIIc. Recent molecular studies have shown considerable polymorphism in the genes for FcγIIc and the functional consequences are being dissected. This appears to include cross-talk between FcγRIIIa and at least some forms of FcγRIIc, which may have important functional consequences.     

细胞因子对异种脱细胞真皮基质免疫调节作用的临床研究

目的　探讨烧伤患者接受异种 /异体脱细胞真皮基质 (xeno /allo ADM )移植后全身和局部多种细胞因子与移植物近期转归的关系。　方法　在大面积烧伤患者的四肢切痂创面上 ,移植xeno ADM (12例 ,19块 )或allo ADM(15例 ,18块 ) ,其上覆盖自体超薄断层皮片 ,并以 6例单纯移植自体中厚断层皮片 (auto TTS)的烧伤患者为对照。移植物成活后 4～ 8周 ,收集局部组织标本、血清和xeno ADM排斥后的创面渗出液 ,采用免疫组织化学染色与酶联免疫吸附法 (ELISA) ,检测白细胞介素 (IL) 1β、IL 4、IL 6、肿瘤坏死因子α(TNF α)和γ型干扰素 (IFN γ)的含量。　结果　免疫组织化学染色结果显示 ,移植物内IL 1β、IL 4、IL 6、TNF α和IFN γ的阳性细胞密度或着色强度相比较 ,xeno ADM >allo ADM >auto TTS (P <0 .0 5 )。ELISA检测结果显示 ,xeno ADM被排斥后创面渗出液中IL 4、IL 6、TNF α和IFN γ水平明显高于自体血清 ,但其血清IL 4与IFN γ水平分别低于和高于未排斥时。xeno ADM移植后血清中IL 4、IFN γ水平明显高于allo ADM和auto TTS(P <0 .0 5～ 0 .0 1)。　结论　xeno ADM移植后可在局部检测到高水平的IL 1β、IL 4、IL 6、IFN γ ,可能与细胞杀伤和细胞因子介导的免疫放大作用有关。这些细胞因子的动态变     

Mechanisms of systemic autoimmunity in murine models of SLE

Our laboratory has utilized spontaneous and experimentally induced models of systemic autoimmunity in mice in order to elucidate the cellular deficiencies in immunoregulation that are essential to this process. In the spontaneously autoimmune mouse strains, genetic defects in T and B cell tolerance are the primary abnormalities that drive the syndrome. The induced chronic graft-vs-host model depends on abnormal T-B interactions resulting from allogeneic recognition of major histocompatibility complex (MHC) class II. Future investigations will target the biochemistry of the loss of tolerance and the specificity of autoreactive T cells that provide help for autoantibody production.     

Expression of interleukin-27 by human trophoblast cells

Cytokines produced at the fetal-maternal interface play a key role in regulating maternal tolerance to the fetus and successful pregnancy. Previously, we showed that EBV-induced gene 3 (EBI3), an interleukin (IL)-12 p40 homologue, was expressed at very high levels by syncytiotrophoblasts and extravillous trophoblasts throughout human pregnancy. EBI3 was recently shown to associate with a novel ligand, p28, to form a new heterodimeric cytokine with important immunoregulatory functions, IL-27. In this study, we investigated whether EBI3 expression by trophoblast cells is associated with that of p28 to form IL-27. We found that genes encoding IL-27 (EBI3 and p28) and its receptor (IL-27R and gp130) were expressed in the placenta at various stages of pregnancy. Co-immunoprecipitation experiments performed from placental lysates, and ELISA of culture supernatants from placental explants, showed that IL-27 heterodimer was produced and released from placental cells. In situ studies of placentae of first, second and third trimester of pregnancy, and of choriocarcinomas, demonstrated that syncytiotrophoblast cells co-expressed EBI3 and p28. Similarly, extravillous trophoblast cells invading the decidua were found to co-express both subunits of IL-27. These data suggest that IL-27 may be part of the cytokine network regulating local immune responses and angiogenesis during human pregnancy.     

烧伤感染对血清中补体C3 和IL-10 水平的影响

目的　分析烧伤感染对血清中补体C3 和IL-10 水平的影响, 旨在根据其变化水平及时给予合适的免疫调节治疗, 预防感染的发生。方法　分别采集患者烧伤后第3、7、14 天的创面分泌物和外周血, 对分泌物做细菌培养, 用酶联免疫吸附测定法(Enzyme-linked immunosorbent assay, ELISA) 检测血清中的补体C3 和IL-10水平, 病情严重疑有脓毒血症者及时进行血培养。结果　烧伤后创面感染率不断上升, 脓毒血症发生率达16.4%, 对补体C3 水平的影响无统计学意义(P >0.05), 但烧伤后第14 天脓毒血症患者血清中IL-10 水平是创面感染患者的2 倍, 相比有统计学意义(P <0.05)。结论　补体C3 水平升高有利于提高机体抵抗力, 但不能反映机体的感染情况; IL-10 水平过度升高对感染加重有一定的预警作用, 在临床判断过程中辅助监测血清中IL-10水平有助于发现感染加重的趋势, 以便及时给予免疫调节治疗。     

T cell subsets in the blast cell population in phytohemagglutinin-stimulated peripheral blood in vitro and in rheumatoid arthritis synovial fluid in vivo

Summary The immunomodulatory T4/T8 ratio was studied in the total and activated lymphocyte populations by a method combining visualisation of ³H-thymidine incorporating blasts with autoradiography (AR) with simultaneous identification of the respective lymphocyte subsets using monoclonal antibodies in avidin-biotin-peroxidase complex (ABC) staining. In rheumatoid arthritis synovial fluid the activated T4/T8 ratio (calculated from T cells in the S phase of the cell cycle) was significantly different from the total T4/T8 ratio (calculated for all the T cells) (0.45±0.05 versus 0.69±0.05, P<0.01). Similarly, the activated and total T4/T8 ratios were also significantly different in the phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cell cultures at days 3 and 5.