OBJECTIVE: To obtain a global view of lymphocyte subset changes in the peripheral blood and cytokine profile in patients with class IV lupus nephritis (LN). METHODS: A total of 30 patients with biopsy proven active class IV LN, 30 patients with biopsy proven active class V LN, and 30 healthy controls were enrolled. Serum concentration of Th1 cytokines (IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed by Fast Quant Human Th1/Th2 protein array. The expression of lymphocyte subsets was measured by flow cytometer. Clinical parameters such as urine protein of 24 h, autoantibodies and complement were detected. Pearson analysis was used to examine the relation between lymphocyte subsets and clinical parameters, cytokine and clinical parameters. RESULTS: The patients with class IV LN had evident anemia (P<0.001), hypocomplementemia, and hypoalbuminemia (P<0.05). There were no significant difference both in the ratio and number of CD4+ lymphocytes between the controls and the patients. In the patients with class IV LN, the ratio and number of CD4+ lymphocytes were both lower than those of the controls (P<0.01). The ratio and number of CD20+ lymphocytes were both higher than those of the controls (P<0.05), and a significant decrease in CD4+CD25+Foxp3+ regulatory T cells (Tregs) was observed in the patients compared with healthy age-matched controls (P<0.001). The abnormality of lymphocytes in class IV patients was obviously notable, especially in CD4+CD25+Foxp3+ regulatory T cells. In class IV patients, most of the detected cytokines levels were markedly elevated as compared with the controls, including Th2 cytokines INF-γ (P<0.05), IL-2 (P<0.05) and TNF-α (P<0.01), and Th2 cytokines IL-4 (P<0.05), IL-6 (P<0.05), IL-10 (P<0.01) and IL-13 (P<0.01). Only 4 out of 9 cytokines significantly increased in class V patients. In addition to IL-2, all of them belonged to Th2 (IL-4, IL-10 and IL-13) cytokines. There was negative correlation between CD4+CD25+Foxp3+ regulatory cells and urine protein, anti-dsDNA titer or SLEDAI (r=-0.781, -0.746 and -0.646, respectively; P<0.05). There was positive correlation between IL-5 and anti-dsDNA titer (r=0.708, P<0.05), between IL-5 and creatinine (r=0.681, P<0.05), and between IL-10 and SLEDAI (r=0.877, P<0.01). There was also negative correlation between IL-10 and urine protein of 24 h (r=-0.659, P<0.05), between IL-10 and hemoglobin concentration (r=-0.856, P<0.01), and between IL-13 and urine protein of 24 h (r=-0.769, P<0.05). There was little correlation between cytokines and clinical parameters in patients with class V LN. CONCLUSION There is extensive abnormality in lymphocyte subsets and cytokine profile in patients with class IV LN, which may be the mechanism of immunosuppressive agents to treat patients with class IV LN.
Cytokines ; immunology ; Flow Cytometry ; Humans ; Interleukin-1 ; Interleukin-10 ; Interleukin-2 ; Interleukin-4 ; Interleukin-5 ; Interleukin-6 ; Lupus Nephritis ; classification ; immunology ; T-Lymphocytes, Regulatory ; immunology ; Tumor Necrosis Factor-alpha

Different functions have been attributed to CD4+CD25+Foxp3+ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-alpha, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.
Aging/*immunology ; Animals ; Cytokines/genetics/metabolism ; Female ; Gene Expression Regulation ; Malaria/*immunology/*parasitology ; Mice ; Plasmodium berghei/*classification ; T-Lymphocytes, Regulatory/classification/*physiology

To study the CTL antigen epitopes and drug resistance mutations of HIV-1 gag and pol genes through analyzing gag and pol gene sequences. The HIV-1 gag and pol gene fragments were amplified using nested polymerase chain reaction. A total of 23 PCR sequences, 449 cloned gag sequences and 402 cloned pol sequences were obtained. Sequence analyses showed the 23 samples were subtype B or B'. A total of 4 in 8 CTL antigen epitopes appeared 8 mutations in consensus sequence of subtype B and B'. There were no mutations found in the PCR sequences, whereas a few mutations were found in clone sequences (9.80%) in 5 antigen epitopes in p24 region. Eighteen PIs-related mutations and 24 RTIs-related mutations were found in PCR sequences and clone sequences in pol gene region, in which 17 (94.44%) PIs-related mutations and 15 (62.50%) RTIs-related mutations were found only in the clone sequences, respectively. The results showed that the prevalence of HIV-1 drug resistance strains in this study was at a higher level (17.39%), suggesting that some samples were resistant.to existing antiviral drugs.
Antigens, Viral ; immunology ; DNA Mutational Analysis ; Drug Resistance, Viral ; genetics ; Epitopes ; immunology ; HIV-1 ; classification ; drug effects ; genetics ; immunology ; Human Immunodeficiency Virus Proteins ; genetics ; Mutation ; Phylogeny ; T-Lymphocytes, Cytotoxic ; immunology ; gag Gene Products, Human Immunodeficiency Virus ; genetics ; pol Gene Products, Human Immunodeficiency Virus ; genetics

M1-type macrophages are capable of inducing lysis in various types of cancer cells, but the mechanism of action is unclear. It has been noted that an "unknown protein" produced together with protease by activated macrophages is responsible for this action. Activated M1 macrophages have been recently reported to produce family 18 chitinases, all of which have been named chitotriosidase. Our experiments have demonstrated that family 18 chitinases work together with proteases and can damage various cancer cells both in vitro and in vivo. Thus, in this article, we suggest that the 50-kDa chitotriosidase is the reported "unknown protein". In addition, we discuss how to properly stimulate activated M1 macrophages to produce 50-kDa chitotriosidases and proteases for destroying cancer cells. Because family 19 chitinase has recently been reported to kill cancer cells, we also discuss the possibility of directly using human family 18 chitotriosidase and the humanized plant family 19 chitinase for cancer treatment.
Animals ; Antineoplastic Agents, Alkylating ; pharmacology ; Chitinases ; metabolism ; Cyclophosphamide ; pharmacology ; Hexosaminidases ; metabolism ; Humans ; Immunosuppressive Agents ; pharmacology ; Macrophage Activation ; immunology ; Macrophages ; classification ; enzymology ; immunology ; pathology ; Neoplasms ; immunology ; pathology ; Peptide Hydrolases ; metabolism ; T-Lymphocytes, Regulatory ; metabolism ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism

OBJECTIVESTo compare the in vitro killing effects of cytotoxic T lymphocytes (CTLs) induced by dendritic cells(DCs) that modified with 4 different specific hAFP-derived peptides.

METHODSDCs derived from normal human peripheral monocytes were activated by GM-CSF and IL-4. MTT assay was applied to analyse the proliferation activities of the DCs. To induce the specific CTLs, DCs modified with four immunodominant epitopes from alpha fetoprotein (AFP) were cocultured with MNC derived CD8+ lymphocytes. The acquired specific CTLs were cocultured with SMMC-7721 cells at different dilutions, and the killing effects were detected by flow-cytometry and Non-Radioactive Cytotoxity kit.

RESULTSThe CTLs stimulated by DCs modified with the four immunodominant epitopes from alpha fetoprotein (AFP) had specific killing activities on the SMMC-7721 cells. And statistical differences of the killing effects existed between the hAFP(158-166) (FMNKFIYEI) group and the other three groups.

CONCLUSIONCTLs induced by the DCs modified with the four immunodominant peptides had significant killing effects on the hepatocellular cancer cells in vitro. The hAFP(158-166) (FMNKFIYEI) peptide had a relatively higher efficiency in inducing DCs and stimulating specific CTLs.

Cell Line, Tumor ; Cell Proliferation ; Cytotoxicity, Immunologic ; Dendritic Cells ; immunology ; Humans ; Peptides ; immunology ; T-Lymphocytes, Cytotoxic ; cytology ; immunology ; alpha-Fetoproteins ; classification ; immunology

Cellular immunity is an important component of human immune system and plays a crucial role in the fight against tumor cell or invasive pathogens. Researches on cell-based immunotherapy have long been focused on eliciting tumor-specific CD8+ cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. However, the resulting treatments have been surprisingly poor at inducing complete tumor rejection, in both the experimental models and clinical trials. The CD4+ T cells has been studied mainly for their role as helpers for CD8+ CTL, even suggesting that the tumor-specific CD4 T regulatory cells could act as suppressors of antitumor responses. Recent studies indicated that CD4+T cells are not a pure cell lineage with single function, but a cell population with complex functions. Moreover CD4+ T cells may not only be helper cells, but also act as potent effector cells or partners with NK cells that can clear a wide variety of tumors. In a word, the antitumor potential of effector CD4+ T cells might have been underestimated. In this article, the classification and differentiation of CD4+ T cells, the function and secreted cytokines of CD4+ T cells, the CD4+ T cells and tumor immune, the tumor-immuno regulatory effects of CD4+ T cells, and clinical researches of CD4+ T cells are reviewed.
CD4-Positive T-Lymphocytes ; classification ; cytology ; immunology ; Cytokines ; metabolism ; Cytotoxicity, Immunologic ; Humans ; Immunity, Cellular

Different subtypes of dendritic cells (DC) influence the differentiation of naive T lymphocytes into T helper type 1 (Th1) and Th2 effector cells. We evaluated the percentages of DC subtypes in peripheral blood from pregnant women (maternal blood) and their cord blood compared to the peripheral blood of healthy non pregnant women (control). Circulating DC were identified by flow cytometry as lineage (CD3, CD14, CD16, CD19, CD20, and CD56)-negative and HLA-DR-positive cells. Subtypes of DC were further characterized as myeloid DC (CD11c+/CD123+/-), lymphoid DC (CD11c-/CD123+++) and less differentiated DC (CD11c-/CD123+/-). The frequency of DC out of all nucleated cells was significantly lower in maternal blood than in control (P<0.001). The ratio of myeloid DC/lymphoid DC was significantly higher in maternal blood than in control (P<0.01). HLA-DR expressions of myeloid DC as mean fluorescence intensity (MFI) were significantly less in maternal blood and in cord blood than in control (P<0.001, respectively). The DC differentiation factors, TNF-alpha and GM-CSF, released from mononuclear cells after lipopolysaccharide stimulation were significantly lower in maternal blood than in control (P<0.01). The distribution of DC subtypes was different in maternal and cord blood from those of non-pregnant women. Their role during pregnancy remains to be determined.
Adult ; Cell Differentiation ; Dendritic Cells/*classification/cytology/immunology ; Female ; Fetal Blood/cytology/*immunology ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; HLA-DR Antigens/metabolism ; Humans ; Lipopolysaccharides/pharmacology ; Lymphocyte Activation ; Pregnancy ; T-Lymphocytes/cytology/immunology ; Th1 Cells/cytology/immunology ; Th2 Cells/cytology/immunology ; Tumor Necrosis Factor-alpha/metabolism

OBJECTIVETo study the characteristics of the virology background of HLA-A2 restricted HBcAg(18-27) epitope mutations in HBV infected patients in China.

METHOD30 HBV sequences with different genotypes from Genbank were analyzed by bioinformatics and the mismatched primers were designed for constructing a PCR-RFLP method to screen HBcAg(18-27)V/I in China. The distributions of HBcAg(18-27)V/I of 160 samples with HBV genotype B/C infection from 8 areas in China were screened and analyzed by PCR-RFLP and sequencing. The affinity of HBcAg(18-27)V/I to HLA-A0201 was analyzed through referencing the bioinformatics websites.

RESULTSWe successfully constructed a PCR-RFLP method for screening HBcAg(18-27)V/I from genotype B/C, and only 3 samples with HBcAg(18-27)V sequence were found in the 160 samples (3/160, 1.88%). The affinity of HBcAg(18-27)I to HLA-A 0201 was lower than the one of HBcAg(18-27)V through bioinformatic analysis (HLA ligand score was 123 vs 156, and the SYFPEITHI score was 22 vs 24).

CONCLUSIONThe last amino acid of most HBcAg(18-27) sequences of epidemic HBV strains in China is isoleucine, and not valine. Therefore HBcAg(18-27) sequence background in different HBV genotypes should be thoroughly considered when using it as a reference or control in immunological research about HBV.

Adult ; China ; epidemiology ; Computational Biology ; DNA, Viral ; genetics ; Epitopes, T-Lymphocyte ; immunology ; Female ; Genotype ; HLA-A Antigens ; immunology ; Hepatitis B Core Antigens ; genetics ; immunology ; Hepatitis B virus ; classification ; immunology ; Hepatitis B, Chronic ; epidemiology ; immunology ; virology ; Humans ; Male ; Mutation ; Sequence Analysis, DNA ; T-Lymphocytes, Cytotoxic ; immunology

Th17(T helper 17 cell), a newly discovered subset of T cells is associated with IL-23 and characterized by production of IL-17, the functions of which are distinct from those of Th1, Th2 and Treg subsets. The development of Th17 cells can be promoted by TGF-beta1, IL-6, and IL-23; but inhibited by IFN-gamma, IL-4 and Socs3. It is clear that Th17 cells have protective effects on body by facilitating the pro-inflammatory responses. On the other hand, the role of Th17 cells in the pathophysiology of autoimmune diseases has been described.
Autoimmune Diseases ; immunology ; physiopathology ; Interleukin-17 ; biosynthesis ; immunology ; Interleukin-23 ; biosynthesis ; genetics ; T-Lymphocyte Subsets ; immunology ; physiology ; T-Lymphocytes, Helper-Inducer ; classification ; cytology ; immunology ; Transforming Growth Factor beta1 ; biosynthesis ; genetics

OBJECTIVETo study the influence of biological characteristics on HCV/HIV co-infection, including HIV-1 sequence distance, HIV-1 viral load and CD4+ count.

METHODSHIV-1 sequence distance was calculated by Clustal W and Phylip software while HIV-1 viral load being tested by NASBA and CD4+ count was tested using Epics XL of Coulter. Significance was determined by t-test using SPSS 12.0.

RESULTSThe mean HIV-1 genetic distances were 7.95% and 15.73% (P < 0.001) between those with HCV co-infection and those without. Their mean HIV-1 viral loads were 4.61 and 4.45 (P = 0.522) and their mean CD4I T counts were 308 and 251 (P = 0.161), respectively.

CONCLUSIONData showed that in the study group, the HIV/HCV co-infection had an influence on the HIV sequence distance, but did not have major impact on HIV-1 viral load and their mean CD4+ T count.

Adult ; Blood Donors ; statistics & numerical data ; CD4-Positive T-Lymphocytes ; immunology ; China ; epidemiology ; Female ; HIV Infections ; epidemiology ; immunology ; virology ; HIV-1 ; classification ; genetics ; immunology ; Hepatitis C ; epidemiology ; immunology ; virology ; Humans ; Male ; Phylogeny