Human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocytes (CTLs) play a critical role in the control of HIV-1 infection and replication. HIV-1 evades CTL mediated pressure through viral escape mutations within targeted CTLs epitopes or flanking regions, but this process is usually associated with a viral fitness cost. The mutated epitopes may weaken the level of the original CTL responses, however, the immune system holds potential to mount denovo responses towards those newly emerged epitopes. This article briefly summarizes recent research progress regarding the competition between HIV-1's escape mutations and host CTL responses.
Animals ; HIV Infections ; genetics ; immunology ; HIV-1 ; genetics ; immunology ; physiology ; Histocompatibility Antigens Class I ; genetics ; immunology ; Humans ; Mutation ; T-Lymphocytes, Cytotoxic ; immunology ; virology

BACKGROUND/AIMS: This study aimed to detect the expression of natural killer (NK) cell receptor natural killer group 2D (NKG2D) in the peripheral blood of patients with primary hepatocellular carcinoma and to discuss the correlation between NK cell cytotoxicity and liver function. METHODS: The number of NK cells and the expression of NK cell receptor NKG2D in peripheral blood were determined by flow cytometry in patients with primary hepatocellular carcinoma, hepatitis B cirrhosis, chronic hepatitis B, and healthy controls. RESULTS: When compared with patients in the healthy and the chronic hepatitis B groups, the primary hepatocellular carcinoma group showed significant decreases in all parameters, including the cytotoxicity of NK cells on K562 cells, expression rate of NKG2D in NK cells, number of NKG2D+ NK cells, expression level of NKG2D, and number of NK cells (p<0.05). The activity of NK cells showed a positive correlation, whereas the Child-Pugh scores in the primary hepatocellular carcinoma and the hepatitis B cirrhosis groups showed a negative correlation with all parameters detected above. CONCLUSIONS: The decrease of NK cell activity in patients with primary hepatocellular carcinoma is closely related to their lower expression of NKG2D. Liver function affects the expression of NKG2D and the activity of NK cells.
Carcinoma, Hepatocellular/*physiopathology ; Case-Control Studies ; Female ; Humans ; K562 Cells ; Killer Cells, Natural/*physiology ; Liver Neoplasms/*physiopathology ; Lymphocyte Subsets/physiology ; Lymphopenia/physiopathology ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; T-Lymphocytes, Cytotoxic/physiology

OBJECTIVETo investigate the effect of protein transduction domain-hepatitis B virus core antigen (CTP-HBcAg18-27)-Tapasin fusion protein-induced specific cytotoxic T lymphocyte (CTL) response on hepatitis B virus (HBV) replication in HBV transgenic mice.

METHODSTwenty HBV-transgenic mice were randomly divided into two groups for a 3-week course of once weekly subcutaneous immunizations with either CTP-HBcAg18-27-Tapasin fusion protein or CTP-HBcAg18-27. Mice administered isotonic saline served as blank controls. Expressions of cytokines in splenocytes were analyzed by flow cytometry. Serum levels of hepatitis B surface antigen (HBsAg) and HBV DNA were determined by microparticle enzyme immunoassay and real-time fluorescent PCR assay, respectively. Expression of HBsAg in hepatic tissues was detected by immunohistochemistry.

RESULTSImmunization with 100 mug of CTP-HBcAg18-27-Tapasin fusion protein led to a significant increase in proportions of CTLs in spleen (2.70%+/-0.20% vs. 50 mug of CTP-HBcAg18-27-Tapasin: 1.66%+/-0.53%, 50 mug of CTP-HBcAg18-27: 1.26%+/-0.56%, and blank controls: 0.75%+/-0.71%; F = 741.45, P = 0.000) and up-regulation of inflammatory cells in hepatic tissue. In addition, both immunizations of CTP-HBcAg18-27-Tapasin led to significant decreases in serum HBsAg and HBV DNA levels compared to those in the CTP-HBcAg18-27 group.

CONCLUSIONHBV-related modification of the expression of the molecular chaperone Tapasin may affect its interaction with intracellular antigen peptides, thereby leading to increases the number of specific CTLs in the spleen, decreases in serum HBsAg and HBV DNA levels, and down-regulation of HBsAg expression in hepatic tissue. These results obtained in HBV-transgenic mice suggest that the CTP-HBcAg18-27-Tapasin fusion protein has anti-HBV activity.

Animals ; DNA, Viral ; blood ; Female ; Hepatitis B ; immunology ; Hepatitis B Core Antigens ; genetics ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; physiology ; Male ; Membrane Transport Proteins ; genetics ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Recombinant Fusion Proteins ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Virus Replication

As a member of the HSP90 family, heat shock protein (HSP) Gp96 is one of the most abundant proteins in the endoplasmic reticulum (ER), which displayed important molecular chaperones function in cells. Gp96 can stimulate the production of cytokines by activating the antigen presentation cells (such as dendritic cell, et al) in innate immunity. It is capable of eliciting an antigen-specific cytotoxic T lymphocyte (CTL) immune response to eliminate pathogens and tumors by facilitating antigen cross-presentation in adaptive immunity. Gp96 is also an ideal adjuvant in many recent researches. Here, we review the progress that addresses the role of biological characteristics, immunogenic mechanism that may be involved in the induction of anti-infection immune response and antitumor immunity, which may guide the new vaccine strategies with the knowledge of Gp96-antigen complexes.
Adjuvants, Immunologic ; genetics ; metabolism ; Antigen-Presenting Cells ; physiology ; Communicable Diseases ; immunology ; Dendritic Cells ; immunology ; Endoplasmic Reticulum ; immunology ; Humans ; Membrane Glycoproteins ; immunology ; Neoplasms ; immunology ; T-Lymphocytes, Cytotoxic ; immunology

OBJECTIVETo explore the immune stimulation effect of recombinant E.coli LLO/OVA on mice bone marrow-derived dendritic cells (BMDCs) and T lymphocytes in vitro.

METHODSAfter BMDCs stimulated by E.coli LLO/OVA, their Toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD) receptor signalling pathway were examined by superarray hybridization; and the priming effect of the vaccine activated BMDCs on CD4(+)T and CD8(+)T was determined by [3H]thymidine uptake and ELISA, the tumor cytotoxic effect of activated CD8(+)T cells was determined by cytotoxic assay.

RESULTSAfter BMDCs were activated by E. coli LLO/OVA via TLR4, NOD1 receptor and NF-κB signalling pathway, the expression of their surface molecules including MHC class I, MHC class II, CD40, CD80 and CD86 significantly up-regulated; the secretion of IL-12 and IFN-γ increased also. The mature BMDCs stimulated the allergic CD4(+)T and CD8(+)T cells proliferation and their IL-2 and IFN-γ secretion, and the activated CD8(+)T cells effectively killed B16-OVA melanoma cells and RMA-S/OVA lymphoma cells in vitro.

CONCLUSIONE.coli LLO/OVA is effective in inducing BMDCs maturation via activating TLR4 and NOD1 receptor signalling pathway and promoting specific anti-tumor T cell immunity in vitro.

Animals ; Antigens, Neoplasm ; genetics ; pharmacology ; Bacterial Toxins ; genetics ; pharmacology ; Cancer Vaccines ; genetics ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; immunology ; Coculture Techniques ; Cytokines ; immunology ; secretion ; Dendritic Cells ; cytology ; drug effects ; immunology ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; genetics ; metabolism ; Female ; Flow Cytometry ; Heat-Shock Proteins ; genetics ; pharmacology ; Hemolysin Proteins ; genetics ; pharmacology ; Immunity, Innate ; drug effects ; Mice ; Mice, Inbred C57BL ; Nod1 Signaling Adaptor Protein ; genetics ; physiology ; Ovalbumin ; genetics ; pharmacology ; Recombinant Fusion Proteins ; genetics ; pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; T-Lymphocytes, Cytotoxic ; drug effects ; immunology ; Toll-Like Receptor 4 ; genetics ; physiology

Untreated human immunodeficiency virus (HIV) infections usually lead to death from AIDS, although the rate of the disease progression varies widely among individuals. The cytotoxic T lymphocyte (CTL) response, which is restricted by highly polymorphic MHC class I alleles, plays a central role in controlling HIV replication. It is now recognized that the antiviral efficacy of CTLs at the single cell level is dependent on their antigen specificity and is important in determining the quality of host response to viruses so that the individual will remain asymptomatic. However, because of the extreme mutational plasticity of HIV, HIV-specific CTL responses are continuously and dynamically changing. In order to rationally design an effective vaccine, the questions as to what constitutes an effective antiviral CTL response and what characterizes a potent antigenic peptide to induce such responses are becoming highlighted as needing to be answered.
Animals ; Antigens, Viral ; immunology ; metabolism ; Epitopes, T-Lymphocyte ; Evolution, Molecular ; Genetic Variation ; HIV Infections ; immunology ; virology ; HIV-1 ; genetics ; pathogenicity ; physiology ; Host-Pathogen Interactions ; Humans ; Immunodominant Epitopes ; T-Lymphocytes, Cytotoxic ; immunology ; metabolism ; virology ; Virus Replication

BACKGROUNDSurvivin is a rather specific gene in tumor tissue. We transfected dendritic cells (DCs) with recombinant adenovirus (Ad) containing survivin gene and granulocyte-macrophage colony-stimulating factor (GM-CSF) gene and tested the inducing effect of the transfected DCs on cytotoxic T lymphocytes (CTL) to kill leukemic cells.

METHODSAfter derived from the peripheral, DCs was assayed by mixed leukocyte reaction (MLR) tests. Lactate dehydrogenase (LDH) release test was used to evaluate cytotoxicity of CTL.

RESULTSExpression of survivin in transfected DCs was confirmed by Western blotting analysis. GM-CSF expression was confirmed by enzyme-linked immunosorbent assay (ELISA). In MLR assay, DCs coinfected with Ad-survivin and Ad-GM-CSF induced higher allogeneic lymphocyte reaction than control DCs at ratios of 1:5, 1:10, 1:50 and 1:100. DCs coinfected with Ad-survivin and Ad-GM-CSF had much higher activity of CTL to HL-60 cells than DCs infected with Ad-survivin only, Ad-GM-CSF only, or control DCs. Levels of interleukin-12 (IL-12) and interferon gamma (IFN-gamma) in lymphocyte supernatants containing DCs coinfected with Ad-survivin and Ad-GM-CSF were significantly higher than those in the control group.

CONCLUSIONDCs coinfected with Ad-survivin and Ad-GM-CSF induce much higher anti-leukemic response in vitro than those infected with either factor. Therefore, adenovirus vectors containing survivin and GM-CSF genes may be promising vaccine candidates for leukemia therapy.

Adenoviridae ; genetics ; Cytotoxicity, Immunologic ; Dendritic Cells ; physiology ; ultrastructure ; Genetic Therapy ; Granulocyte-Macrophage Colony-Stimulating Factor ; genetics ; HL-60 Cells ; Humans ; Inhibitor of Apoptosis Proteins ; Interferon-gamma ; biosynthesis ; Interleukin-12 ; biosynthesis ; Leukemia ; therapy ; Lymphocyte Activation ; Microtubule-Associated Proteins ; genetics ; Neoplasm Proteins ; genetics ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection

OBJECTIVETo characterize HIV-1 specific CTL responses to regulatory proteins Tat and Rev in HIV-B'/C virus-infected ART-naive individuals.

METHODSHIV-1-specific CTL responses were analyzed by IFN-gamma ELISPOT assay using overlapping peptides spanning the consensus sequences of HIV-1 clade C Tat and Rev proteins. Statistical analysis and graphical presentation were performed using SIGMAPLOT 10.0 and SIGMASTAT 3.5. For samples with a positive response, the magnitude of CTL responses was compared between HIV-1 C proteins by Wilcoxon rank sum test, and the significance threshold was P<0.05.

RESULTSTat and Rev were frequently recognized, with 23% and 52% of the tested individuals having detectable responses to these proteins, respectively. Several immunodominant regions were detected in Rev. No significant correlation was observed between the magnitude and breadth of CTL responses to regulatory proteins and the control of virus replication in this study.

CONCLUSIONTat and Rev can serve as targets for HIV-1-specific CTL, and several immunodominant regions are detectable in Rev. Further characterization of epitopes and their role in virus control may shed light on pathogenesis of HIV-1 natural infection and also be useful for the design and testing of candidate vaccines.

Amino Acid Sequence ; Gene Products, rev ; immunology ; Gene Products, tat ; immunology ; HIV ; physiology ; HIV Infections ; immunology ; Humans ; Molecular Sequence Data ; T-Lymphocytes, Cytotoxic ; immunology ; Virus Replication

Animals ; Epitopes, T-Lymphocyte ; immunology ; Equine Infectious Anemia ; immunology ; virology ; Horses ; Infectious Anemia Virus, Equine ; immunology ; physiology ; T-Lymphocytes, Cytotoxic ; immunology ; physiology

This study was purposed to investigate the changes in quantum and function of gammadelta T cell subsets, and to explore its significance in pathogenesis of acquired pure red cell aplastic anemia (A-PRCA). Eleven patients were diagnosed as A-PRCA based on bone marrow smear and biopsy, and were treated with cyclosporine A and glucosidorum tripterygll totorum. The flow cytometry technique was used for analyses of T cells subsets and gammadelta T cells. Furthermore, peripheral mononuclear cells (MNC) isolated from A-PRCA patients were cultured in RPMI 1640 medium (10(5) cells/ml) containing 10% FCS, phytohemagglutinin (PHA, 10 microg/ml), and recombinant human interleukin-2 (rIL-2, 50 U/ml) for two weeks, then gammadelta T cells were isolated with the TCRgammadelta Microbead Kit from cultured cells. The collected gammadelta T cells were incubated with normal control bone marrow MNC in RPMI 1640 medium (37 degrees C, 5% CO2 atmosphere) for CFU-E, CFU-GM, and BFU-E colony assay. The result showed that compared with the control group, CD3(+), CD8(+) cells increased significantly in the patient group (P < 0.05), the CD4(+)/CD8(+) ratio decreased and reversed, and gammadelta T cells were significantly increased in patient group (P < 0.05). After treatment with cyclosporine A, 9 out of 11 patients got good response, and CD3(+), CD8(+) cells in the responding patient decreased, the ratio of CD4(+)/CD8(+) returned to normal, and gammadelta T cells also decreased to normal range. Moreover, in vitro culture, the gammadelta T cells isolated from A-PRCA patients showed an inhibiting action to CFU-E and BFU-E but not to CFU-GM in a dose-dependent manner. It is concluded that gammadelta T cells increase in A-PRCA patients, and decrease in parallel to normal range with significant improvement of anemia symptoms after immune suppressive therapy. The gammadelta T cells isolated from A-PRCA patients showed an inhibiting action to CFU-E and BFU-E but not to CFU-GM in vitro culture, suggesting that gammadelta T cells may bring an impact on the research of A-PRCA pathogenesis. Cyclosporine A demonstrated better therapeutic effect on A-PRCA patients.
Adult ; Aged ; CD4-CD8 Ratio ; Cells, Cultured ; Cyclosporine ; therapeutic use ; Female ; Flow Cytometry ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Middle Aged ; Receptors, Antigen, T-Cell, gamma-delta ; physiology ; Red-Cell Aplasia, Pure ; drug therapy ; etiology ; immunology ; T-Lymphocyte Subsets ; cytology ; T-Lymphocytes ; cytology ; T-Lymphocytes, Cytotoxic ; immunology