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Anti-CD3 Antibody Induces IL-10-producing CD4+CD25+ Regulatory T Cells, Which Suppress T Cell Response in Rheumatoid Arthritis Patients.

Bo Young YOON ; Mi La CHO ; Yeon Sik HONG ; Joo Yeon JHUN ; Mi Kyung PARK ; Kyung Su PARK ; Sung Hwan PARK ; Ho Youn KIM

Immune Network.2007;7(3):124-132. doi:10.4110/in.2007.7.3.124

BACKGROUND: Regulatory T cells (Tregs) have been investigated intensively for some decades. These cells regulate the immune system, prevent overactivated immune responses and can be used therapeutically. For rheumatoid arthritis (RA), understanding the functions and status of Tregs is an important step for understanding immune regulation in this autoimmune disease. METHODS: We investigated the percentages, phenotypes and suppressive functions of CD4+CD25+ Tregs in peripheral blood (PB) of patients with RA. RESULTS: The percentages were higher in the patients (n=12) than in healthy controls (n=10), and the cells expressed the CD45RBlow, CTLA-4 and CCR7 phenotypes. We also investigated the expression of Foxp3 and secretion of interleukin (IL)-10 induced CD4+CD25+ Tcells by anti-CD3 antibody treatment. A suppressive function of the patients' cells was shown through coculture with CD4+CD25+ T cells in vitro. CONCLUSION: We suggest that, despite their increased numbers and suppressive function, they manage the ongoing inflammation ineffectively. It might be possible to apply IL-10 to induce the proliferation of IL-10-producing Tregs as therapy for RA.
Arthritis, Rheumatoid* ; Autoimmune Diseases ; Coculture Techniques ; Humans ; Immune System ; Inflammation ; Interleukin-10 ; Interleukins ; Phenotype ; T-Lymphocytes ; T-Lymphocytes, Regulatory*

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Hepatocyte Growth Factor is the Key Cytokine in Stimulating Potential Stem Cells in the Cord Blood into Hepatic Lineage Cells.

Kyung Ha RYU ; Su Jin CHO ; So Youn WOO ; Ju Young SEOH ; Yun Jae JUNG ; Ho Seong HAN

Immune Network.2007;7(3):117-123. doi:10.4110/in.2007.7.3.117

BACKGROUND: This study was designed to investigate the role of the hepatocyte growth factor (HGF) with regards to differentiation of somatic stem cells originating from the human umbilical cord blood (UCB) into hepatic lineage cells in vitro culture system. METHODS: Mononuclear cells from UCB were cultured with and without HGF based on the fibroblast growth factor (FGF)-1, FGF-2, and stem cell factor. The cultured cells were confirmed by immunofluorescent staining analysis with albumin (ALB), cytokeratin-19 (CK-19), and proliferating cell nuclear antigen (PCNA) MoAb. ALB and CK-18 mRNA were also evaluated by reverse transcription-polymerase chain reaction. In order to observe changes in proliferating capacity with respect to the cultured period, CFSE with affinity to proliferating cells were tagged and later underwent flow cytometry. RESULTS: In the HGF-treated group, cultured cells had a large oval shaped appearance with adherent, but easily detachable characteristics. In the HGF-non treated group, these cells were spindle-shaped with strong adherent characteristics. Expressions of ALB and CK-19 were evident in HGF-treated group compared to non-expression of those in to HGF-non treated group. Dual immunostaining analysis of the ALB producing cells showed presence of PCNA in their nuclei, and ALB and CK-18 mRNA were detected on the 21st day of cultured cells in the HGF-treated group. CONCLUSION: Our findings suggest that HGF has a pivotal role in differentiating somatic stem cells of human UCB into hepatic lineage cells in vitro.
Cells, Cultured ; Fetal Blood* ; Fibroblast Growth Factor 2 ; Fibroblast Growth Factors ; Flow Cytometry ; Hepatocyte Growth Factor* ; Hepatocytes* ; Humans ; Keratin-19 ; Proliferating Cell Nuclear Antigen ; RNA, Messenger ; Stem Cell Factor ; Stem Cells*

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B Cells Transduced with HPV16 E6/E7-expressing Adenoviral Vector Can Efficiently Induce CTL-dependent Anti-Tumor Immunity.

Yun Sun KIM ; Hyun Jeong KO ; Yeon Jeong KIM ; Seung Hee HAN ; Jung Mi LEE ; Woo Sung CHANG ; Hyun Tak JIN ; Young Chul SUNG ; Chang Yuil KANG

Immune Network.2007;7(3):109-116. doi:10.4110/in.2007.7.3.109

BACKGROUND: Human papillomavirus (HPV) infection is responsible for cervical cancer, a common cancer in women. Since HPV infection and cancer development are controlled by the host immune system, immunotherapy against HPV can be helpful in preventing or treating HPV-associated cervical cancer. Two oncoproteins of HPV16, E6 and E7, are promising targets for immunotherapy against cervical cancer, because they are constitutively expressed in cervical cancer. METHODS: Since cellular vaccines using B cells as well as dendritic cells offer an efficient approach to cancer immunotherapy, we opted to use B cells. We evaluated the immunogenicity and anti-tumor effects of a B cell vaccine transduced with HPV16 E6/E7-expressing adenovirus. RESULTS: Vaccination with HPV16 E6/E7-transduced B cells induced E6/E7-specific CD8+ T cell-dependent immune responses and generated anti-tumor effects against E6/E7-expressing TC-1 tumor. The anti-tumor effect induced by this B cell vaccine was similar to that elicited by DC vaccine, showing that B cells can be used as an alternative to dendritic cells for cellular vaccines. CONCLUSION: Thisstudy has shown the feasibility of using B cells as immunogenic APCs and the potential for developing prophylactic and therapeutic vaccines against HPV-associated cervical cancer using a B cell vaccine transduced with adenovirus expressing HPV16 E6/E7.
Adenoviridae ; B-Lymphocytes* ; Dendritic Cells ; Female ; Humans ; Immune System ; Immunotherapy ; Oncogene Proteins ; Uterine Cervical Neoplasms ; Vaccination ; Vaccines

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Study on the expression and detection of the p53 mutation in Korean colon cancer cell lines.

Ji Yeon JUNG ; Sang Jin OH

Immune Network.2001;1(2):151-161. doi:10.4110/in.2001.1.2.151

BACKGROUND: Inactivation in p53 tumor suppressor gene through a point mutation and deletion is one of the most frequent genetic changes found in human cancer, with 50% of an incidence. This high rate of mutation mostly suggests that the gene plays a central role in the development of cancer and the mutations detected so far were found in exons 5 to 8. Mutation of p53 locus produced accumulation of abnormal p53 protein, and negative regulation of cell proliferation and transcriptional activation as a suppressor of transformation were lost . In addition, inhibition of its normal cellular function of wild-type by mutant is an important step in tumorigenesis. METHOD: 4 colon cancer cell lines (SNU C1, C2A, C4, C5) were examined for mutation in exons 5 to 8 of the p53 tumor suppressor gene by PCR-SSCP analysis and expression pattern by western blotting and immunoprecipitation. p53-mediated transactivation ability were examined by CAT assay and base substitution of p53 in SNU C2A cell were detected by DNA sequencing. RESULTS: 1) SNU C2A cell and SNU C5 cell were detected mobility shifts each in exon 5 and exon 7 of p53 gene by the PCR-SSCP method, implicating being of p53 mutation. 2) 3 colon cancer cell lines (SNU C1, SNU C2A, SNU C5) expressed wild type and mutant type p53 protein. 3) In northern blot experiment, SNU C2A and SNU C5 cell expressed high level of p53 mRNA. 4) Results of p53-mediated transactivation in colon cancer cell lines by CAT assay represented only SNU C2A cell has transcriptional activity. 5) DNA sequencing in SNU C2A cell showed missense mutation in codon 179 of one allele, histidine to arginine and wild type p53 in the other allele. CONCLUSION: Colon cancer cell lines showed correlation with mutation in p53 gene and accumulation of abnormal p53 protein. Colon cancer cell SNU C2A retained p53-mediated transactivation as heterozygous p53 with one mutant allele in 179 codon and the other wild-type allele.
Alleles ; Animals ; Arginine ; Blotting, Northern ; Blotting, Western ; Carcinogenesis ; Cats ; Cell Line* ; Cell Proliferation ; Codon ; Colon* ; Colonic Neoplasms* ; Exons ; Genes, p53 ; Genes, Tumor Suppressor ; Histidine ; Humans ; Immunoprecipitation ; Incidence ; Mutation, Missense ; Point Mutation ; RNA, Messenger ; Sequence Analysis, DNA ; Transcriptional Activation

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Study of plasma transforming growth factor-beta 1 level as a useful tumor marker in various cancers.

Hoon SHIN ; Chang Ki LIM ; In Young CHOI ; Doo Yun LEE ; Dong Yong NOH ; Min Hee RYU ; Hyo Suk LEE ; Yung Jue BANG ; Jong Sup PARK ; Seung Won JIN

Immune Network.2001;1(2):143-150. doi:10.4110/in.2001.1.2.143

BACKGROUND: Many investigators have found transforming growth factor-1 (TGF-1) to be elevated in tumors. Changes in responsiveness to TGF-1 have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-1. However, a little is known about the association of TGF-1 with progression of malignant tumor. METHODS: In this study, we measured the plasma level of TGF-1 in various cancer patients and evaluated the utility of plasma TGF-1 as a possible tumor marker. Plasma TGF-1 levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-1 in the aspects of sensitivity and specificity. RESULTS: The mean of plasma TGF-1 levels was 1.2 19 +/-0.834 ng/ml in normal controls, 5.491 +/-3.598 ng/ml in breast cancer, 12.670 +/-10.386 ng/ml in lung cancer, 5.747 +/-3.228 ng/ml in hepatocellular carcinoma and 10.854 +/-7.996 ng/ml in cervical cancer. In comparison with CEA and AFP, TGF-1 is more sensitive. CONCLUSION: We conclude that the high levels of TGF-1 are common in the plasma of cancer patients. These result s suggest that the plasma TGF-1 level can be a potent tumor marker in various cancer patients.
alpha-Fetoproteins ; Breast Neoplasms ; Carcinoembryonic Antigen ; Carcinoma, Hepatocellular ; Cell Line ; Enzyme-Linked Immunosorbent Assay ; Humans ; Lung Neoplasms ; Plasma* ; Research Personnel ; Sensitivity and Specificity ; Uterine Cervical Neoplasms

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Association of HIV infection with MICA (MHC class I chain-related A) gene alleles.

Moon Won KANG ; Seong Heon WIE ; Yang Ree KIM ; Joo Shil LEE ; Chul Woo PYO ; Hoon HAN ; Tai Gyu KIM

Immune Network.2001;1(2):135-142. doi:10.4110/in.2001.1.2.135

BACKGROUND: A large number of diseases occur in association with specific HLA-B or-C alleles. Recently a new gene, termed maj or histocompatibility complex class I chain-related gene A (MICA), has been identified in close proximity to HLA-B. The function of this gene is still unknown. However, it is structurally similar to HLA class I genes. MICA gene is polymorphic and is potentially associated with several diseases. METHODS: To evaluate the association of MICA gene in Korean patient s with human immunodeficiency virus 1 (HIV-1) infections, Polymerase chain reaction-Sequence specific primer (PCR-SSP) was done for MICA alleles in the extracellular exons, and a microsatellite analysis for GCT repeat polymorphisms in the TM exon was also completed. RESULTS: In 199 Korean healthy controls, 7 alleles were observed and the frequencies for each allele were MICA008 (44.7%), MICA0 10 (34.2%), MICA002 (31.7%), MICA004 (23.6%), MICA0 12 (2 1.6%), MICA009 (19.6%), and MICA007 (6.5%). When 65 HIV seropositive patients were analyzed, MICA007 allele frequency was significantly higher than in controls (15.4% vs 6.5 %, RR=2.6, p<0.04). In contrast, the frequencies of other MICA alleles and microsatellite alleles in the transmembrane region of MICA gene were not significantly different between HIV seropositive patients and controls. The tight linkage between MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon was observed as follows; MICA002/A9, MICA004/A6, MICA007/A4, MICA008/A5. 1, MICA0 10/A5, and MICA0 12/A4 in both groups. No significant difference between patient s and controls was observed in the haplotype frequencies of MICA alleles in the extracellular exons and GCT repeat polymorphisms in the TM exon. CONCLUSION: The data suggest that immune functions related with MICA gene may affect a HIV infections.
Alleles ; Exons ; Gene Frequency ; Genes, MHC Class I ; Haplotypes ; HIV Infections* ; HIV* ; HIV-1 ; HLA-B Antigens ; Humans ; Major Histocompatibility Complex ; Microsatellite Repeats

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Characteristics of B Cell proliferation by polysaccharide fraction of Paeonia japonica miyabe.

Hae Ran PARK ; Yeon Ho HAM ; Sung Tae YEE ; Sang Gi PAIK ; Sung Kee JO

Immune Network.2001;1(2):126-134. doi:10.4110/in.2001.1.2.126

BACKGROUND: Paeonia j ap onica Miyabe is a medicinal plant which has been widely used as a component of blood-building decoctions (Chinese medicinal concept : Bu-Xie). The immunopharmacological characteristics of the extract of Paeonia j ap onica (PJ) were investigated. METHODS: The effects of fractions of PJ extract on lymphocyte proliferation were measured by H3 -thymidine incorporation assay . The proliferated lymphocyte subsets were analyzed in flow cytometry . The subset cell populations of spleen cells were separated by magnetic cell separation system, and their proliferation by the extract were investigated. The effect of the extract on antibody production was determined in mice challenged with sheep red blood cells (SRBC) using hemolytic plaque forming cell assay. RESULTS: Spleen cells were proliferated by water extract of PJ. Polysaccharide fraction (PJ-P) of the extract was most active in the proliferation. It was found in flow cytometry that the lymphocyte subset proliferated by PJ-P was B cell population. Among the separated subset cell populations, T cell-depleted cell population and macrophage-depleted cell population were most proliferated by PJ-P. However, positively selected populations of B cells and T cells were not proliferated by PJ-P. These result s indicate that B cell proliferation by PJ-P may require the assistance of macrophages or T cells. These result s suggest that firstly PJ-P may stimulate macrophages or T cells, and then B cells are activated. The number of antibody-secreting cells was increased by administration of PJ-P in mice immunized with SRBC as a T-dependent antigen. CONCLUSION: These result s suggest that macrophages and accessory cells are directly activated by PJ-P and then helper T cells and B cells are indirectly activated. As the results, immune responses might be coordinately improved. In conclusion, PJ-P, a polysaccharide of P. j ap onica, may be a characteristic immunostimulator, which is analogous to polysaccharides such as lentinan, PSK and ginsan.
Animals ; Antibody Formation ; Antibody-Producing Cells ; B-Lymphocytes ; Cell Proliferation* ; Cell Separation ; Erythrocytes ; Flow Cytometry ; Lentinan ; Lymphocyte Subsets ; Lymphocytes ; Macrophages ; Mice ; Paeonia* ; Plants, Medicinal ; Polysaccharides ; Sheep ; Spleen ; T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Water

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Nitric oxide-induced immune switching in experimental inflammatory autoimmune diseases.

Hyun Jeong KWAK ; Hyung Jin KIM ; Jae Sung PARK ; Chang Duk JUN ; Mun Young LEE ; Tae Kyun SHIN ; Hun Taeg CHUNG

Immune Network.2001;1(2):116-125. doi:10.4110/in.2001.1.2.116

BACKGROUND: Nitric oxide (NO) production has been described as a double-edged sword eliciting both pro-and anti-inflammatory effect s in different immune reactions. This work was undertaken to investigate the immunoregulatory role of NO in experimental allergic encephalomyelitis (EAE) and experimental allergic uveitis (EAU). MEHHOD: We examined whether molsidomine (MSDM), a NO donor, administration to the myelin basic protein (MBP)-or interphotoreceptor retinoid binding protein (IRBP)-immunized rat s could suppress EAE development by shifting toward the Th2 cytokine response. In the EAE experiment s, the rat s were treated orally with MSDM (10 mg/kg/day) at the early stage (-1-4 days) or throughout the experimental period (-1-15 days). RESULTS: This resulted in significant amelioration of the disease and mild clinical symptoms, while MBP-immunization without MSDM administration showed severe EAE development . A marked reduction in inflammation was also observed in the spinal cord, indicating the crucial role of NO in the pathogenesis of EAE in in vivo. In the EAU experiments, a 24 h pre-treatment with MSDM prior to IRBP immunization resulted in significant inhibition of the disease. Furthermore, MSDM administration for 2 1 days completely reduced the incidence and severity of EAU. To investigate whether MSDM could modulate cytokine switching from Th 1 to Th2, culture supernatants of MBP-or IRBP-stimulated inguinal lymphocytes were analyzed. MSDM treatment enhanced IL-10 secretion but decreased IFN-gamma. IL-4 was undetectable in all groups. In contrast, the MBP-or IRBP-immunized rat s without MSDM secreted high concentrations of IFN-gamma, but low concentrations of IL-10. CONCLUSION: In conclusion, NO administation suppresses EAE and EAU by modulating the Th 1/Th2 balance during inflammatory immune responses. This work further suggest s that NO may be useful in the therapeutic control of autoimmune disease.
Animals ; Autoimmune Diseases* ; Carrier Proteins ; Encephalomyelitis, Autoimmune, Experimental ; Humans ; Immunization ; Incidence ; Inflammation ; Interferon-gamma ; Interleukin-10 ; Interleukin-4 ; Lymphocytes ; Molsidomine ; Myelin Basic Protein ; Nitric Oxide ; Nitric Oxide Synthase Type II ; Rats ; Spinal Cord ; Tissue Donors ; Uveitis

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Interferon consensus sequence binding protein: Not essential for interferon alpha-mediated antiviral response to vesicular-stomatitis virus infection in HL-60 cells.

Byung Kiu PARK

Immune Network.2001;1(2):109-115. doi:10.4110/in.2001.1.2.109

BACKGROUND: The role of the interferon consensus sequence binding protein (ICSBP), a member of interferon regulatory factor family, in protecting against a vesicular stomatitis virus (VSV) infection has not been firmly elucidated. Thus, it was investigated utilizing the human promyelocytic leukemia HL-60 cells which do not express ICSBP. METHODS: HL-60 cells were stably transfected with plasmid containing cDNA for either ICSBP or DNA binding domain (DBD) and tested for their VSV-susceptibilities. The susceptibility of each transfectant group to a VSV infection was determined by a plaque assay at 1 h, 24 h, and 48 h post-infection in the presence (500 IU/ml) or absence of interferon alpha(IFN alpha). RESULTS: In the absence of IFN alpha, the three groups showed similar sensitivities to a VSV infection. However, when pre-treated with IFN, the viral titers in both the ICSBP and control clones steadily decreased over 48 h of incubation, indicating the existence of IFN alpha-mediated protection against VSV infection. The IFN alpha-treated ICSBP clones appeared to be more resistant to infection compared with the control clones, although the difference was not great . On the contrary, the viral titers in the IFN alpha-treated DBD clones increased at 24 h then decreased by 48 h. CONCLUSION: The expression of truncated ICSBP (DBD) does not appear to underlie the impaired protection against a VSV infection in the DBD clones, since even the control clones lacking ICSBP were protected from a VSV infection. This suggests that ICSBP does not play a critical role in the IFN alpha-mediated anti-VSV response of HL-60 cells, although it appears to confer some resistance to a VSV infection.
Carrier Proteins* ; Clone Cells ; Consensus Sequence* ; Consensus* ; DNA ; DNA, Complementary ; HL-60 Cells* ; Humans ; Interferon-alpha ; Interferons* ; Leukemia ; Plasmids ; Vesicular Stomatitis

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Mechanism of aging and prevention.

Jay Sik KIM

Immune Network.2001;1(2):104-108. doi:10.4110/in.2001.1.2.104

Aging is a senescence and defined as a normal physiologic and structural alterations in almost all organ systems with age. As Leonard Hayflick, one of the first gerontologist s to propose a theory of biologic aging, indicated that a theory of aging or longevity satisfies the changes of above conditions to be universal, progressive, intrinsic and deleterious. Although a number of theories have been proposed, it is now clear that cell aging (cell senescence) is multifactorial . No single mechanism can account for the many varied manifestations of biological aging. Many theories have been proposed in attempt to understand and explain the process of aging. Aging is effected in individual by genetic factors, diet, social conditions, and the occurrence of age-related diseases as diabetes, hypertension, and arthritis. It involves an endogenous molecular program of cellular senescence as well as continuous exposure throughout life to adverse exogenous influences, leading to progressive infringement on the cell's survivability so called wear and tear. So we could say the basic mechanism of aging depends on the irreversible and universal processes at cellular and molecular level. The immediate cause of these changes is probably an interference in the function of cell's macromolecules-DNA, RNA, and cell proteins-and in the flow of information between these macromolecules. The crucial questions, unanswered at present, concerns what causes these changes in truth. Common theories of aging are able to classify as followings for the easy comprehension. 1. Biological, 1) molecular theories-a. error theory, b . programmed aging theory, c. somatic mutation theory, d. transcription theory, e. run-out-of program theory, 2) cellular theories-a. wear and tear theory, b . cross-link theory, c. clinker theory, d. free radical theory, e. waste product theory, 3) system level theory-a. immunologic/autoimmune theory, 4) others-a. telomere theory, b . rate of living theory, c. stress theory, etc. Prevention of aging is theoretically depending on the cause or theory of aging. However no single theory is available and no definite method of delaying the aging process is possible by this moment . The most popular action is anti-oxidant therapy using vitamin E and C, melatonin and DHEA, etc. Another proposal for the reverse of life-span is TCP-17 and IL-16 administration from the mouse bone marrow B cell line study for the immunoglobulin VDJ rearrangement with RAG-1 and RAG-2. Recently conclusional suggestion for the extending of maximum life-span thought to be the calory restriction.
Aging* ; Animals ; Arthritis ; Bone Marrow ; Cell Aging ; Cell Line ; Comprehension ; Dehydroepiandrosterone ; Diet ; Hypertension ; Immunoglobulins ; Interleukin-16 ; Longevity ; Melatonin ; Mice ; RNA ; Social Conditions ; Telomere ; Vitamin E ; Vitamins ; Waste Products

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