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1.
Yamaji K Nabeshima S Murata M Chong Y Furusyo N Ikematsu H Hayashi J 《Cancer immunology, immunotherapy : CII》2006,55(4):394-403
Type I interferon (IFN) possesses antiviral and antitumor activities and also having an immune regulatory effect, activating
cellular immune response and upregulating several cytokines. Recent study has shown that type I IFN upregurates the dendritic
cell production of IL-15 capable of activating natural killer cells and CD8+ memory T lymphocytes. However, it is still unknown if type I IFN induces IL-15 production in non-immune cells and if type
I IFN affects IL-15 production in vivo. The present study investigated the effect of type I IFNs on IL-15 expression in hepatocellular
carcinoma (HCC) cell lines in vitro and in patients with chronic hepatitis C in vivo. When three HCC cell lines, Huh7, HepG2,
and JHH4 were cultured in vitro, IFN upregulation of IL-15 expression was observed at both the mRNA and protein levels. In
experiments using Huh7 cells, upregulation of IL-15 expression occurred within 24 h of the start of IFN stimulation, and both
IFN-α and -β dose-dependently increased IL-15 production in the range from 100 U/ml to 10,000 U/ml of concentration. IFN-β
showed stronger activity in IL-15 production induction in vitro than IFN-α. For in vivo examination, sera were obtained from
21 chronic hepatitis C patients treated with IFN and 29 healthy individuals, and the serum IL-15 level was quantified by ELISA.
The serum IL-15 level of chronic hepatitis C patients before IFN treatment was similar to that of the healthy controls and
significantly increased only during the IFN administration period. These results confirm that IFN-α/β induce IL-15 production
and also suggest that IL-15 may be associated with type I IFN-induced immune response. 相似文献
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3.
The mouse model of genital herpes relies on medoxyprogesterone treatment of female mice to render the vaginal lumen susceptible to inoculation with herpes simplex virus 2 (HSV-2). In the present study, we report that mice deficient in the A1 chain of the type I interferon receptor (CD118(-/-)) are susceptible to HSV-2 in the absence of medroxyprogesterone preconditioning. In the absence of hormone pretreatment, 2,000 PFU of a clinical isolate of HSV-2 was sufficient to establish a productive infection in the vagina of 75% ± 17% and in the spinal cord of 71% ± 14% of CD118(-/-) mice, whereas the same dose of HSV-2 replicated to detectable levels in only 13% ± 13% of vaginal samples and 0% of spinal cord samples from wild-type mice, as determined at day 5 postinfection. The susceptibility to HSV-2 infection in the CD118(-/-) mice was associated with a significant reduction in the infiltration of HSV-specific cytotoxic T lymphocytes into the vaginal tissue, the local production of gamma interferon (IFN-γ), and the expression of T cell-recruiting chemokines CCL5, CXCL9, and CXCL10. Collectively, the results underscore the significant contribution of type I IFNs in resistance to genital HSV-2 infection. 相似文献
4.
Production of interferons and change of the lymphocyte subpopulation phenotype in peripheral blood at cervical papillomavirus infection 总被引:3,自引:0,他引:3
Lazarenko L Spivak M Lakatosh V Kryvokhatska L Mikhailenko O Rudenko A Tkáciková L Mikula I 《Folia microbiologica》2002,47(6):747-752
IFN-γ and IFN-α productionin vitro by peripheral blood cells activated by phytohemagglutinin or the Newcastle disease virus was impaired in patients with a
benign process, cervical intraepithelial neoplasm and cancerin situ associated with human papillomavirus infection. In case of IFN-γ and IFN-α production impairment following cervical papillomavirus
infection, the increased severity of disease was accompanied by remarkable IFN system suppression. The lower synthesis of
both IFN correlated with changes of some lymphocyte-subpopulation phenotype in peripheral blood. Lower CD4+ and CD3+ DR+ T cell concentrations were observed in papillomavirus-infected patients with impaired IFN production; impaired IFN-γ production
was accompanied by lower CD4/CD8 index. 相似文献
5.
R. K. Saxena Q. B. Saxena T. L. Whiteside R. H. Goldfarb R. B. Herberman 《Journal of biosciences》1996,21(1):13-25
A cytokine which augments the expression of major histocompatibility complex (MHC) I antigens on K562 and gastric carcinoma
tumour (HR) cells, has been isolated from the culture supernatant of Concanavalin-A (Con-A) activated human peripheral blood
mononuclear cells. The factor, termed MHC augmenting factor (MHC- AF) has been partially purified by Sephadex G- 100 column
chromatography, preparative isoelectric focusing and HPLC with ion- exchange as well as sizing columns. MHC-AF activity is
associated with a 35 kDa molecule which has pI of 6.0. Interferon (IFN)-α, \, tumour necrosis factor (TNF), Interleukin (IL)-2,
IL-4, IL-5 and IL-7 had no significant effect in MHC- AF bioassay, but IFN-γ had significant MHC-AF activity. Antibodies to
IFN-α, IFN-\ and TNF-α did not block the activity of MHC-AF, but anti-IFN-y antibodies could partially neutralize the activity.
However, unlike IFN-γ, MHC-AF activity was resistant to pH 2.0 treatment. Purified MHC-AF preparations did not have any activity
in WISH cell/encephalo myocarditis virus (EMC) IFN bioassays. In addition, anti-IFN-y affinity column did not retain MHC-AF
activity. These results indicate that a MHC-AF distinct from IFN-γ, is produced by activated human mononuclear cells. 相似文献
6.
Danielle Burger 《Arthritis research & therapy》2000,2(6):472-5
The intricate interactions that regulate relationships between endogenous tissue cells and infiltrating immune cells in the rheumatic joint, particularly in rheumatoid arthritis (RA), were the subject of the meeting. A better understanding of these interactions might help to define intervention points that could be used to develop specific therapies. The presentations and discussions highlighted the fact that, once chronic inflammation is established, several pro-inflammatory loops involving tumour necrosis factor (TNF)-α and interleukin (IL)-1β can be defined. Direct cellular contact with stimulated T lymphocytes induces TNF-α and IL-1β in monocytes which in turn induce functions in fibroblast-like synoviocytes. The latter include the production of stromal cell-derived factor-1α (SDF-1α) which enhances the expression of CD40L in T cells, which stimulates SDF-1α production in synoviocytes, which in turn protects T and B cells from apoptosis and enhances cell recruitment thus favoring inflammatory processes. IL-1β and TNF-α also induce IL-15 in fibroblast-like synoviocytes, which induces the production of IL-17 which in turn potentiates IL-1β and TNF-α production in monocyte-macrophages. This underlines the importance of TNF-α and IL-1β in RA pathogenesis, and helps explain the efficiency of agents blocking the activity of these cytokines in RA. Factors able to block the induction of cytokine production (such as apolipoprotein A-I [apo A-I] and interferon [IFN]-β) might interfere more distally in the inflammatory process. Furthermore, stimulated T lymphocytes produce osteoclast differentiation factor (ODF), which triggers erosive functions of osteoclasts. Therefore, factors capable of affecting the level of T lymphocyte activation, such as IFN-β, IL-15 antagonist, or SDF-1α antagonist, might be of interest in RA therapy. 相似文献
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8.
Wujiang Liu Michael A. O’Donnell Xiaohong Chen Ruifa Han Yi Luo 《Cancer immunology, immunotherapy : CII》2009,58(10):1647-1655
Purpose The proper induction of cellular immunity is required for effective bacillus Calmette-Guérin (BCG) immunotherapy of bladder
cancer. It has been known that BCG stimulation of human peripheral blood mononuclear cells (PBMC) leads to the generation
of effector cells cytotoxic to bladder cancer cells in vitro. To improve BCG therapy, we previously developed human interferon
(IFN)-α 2B secreting recombinant (r) BCG (rBCG-IFN-α). We demonstrated that rBCG-IFN-α augmented T helper type 1 (Th1) cytokine
IFN-γ production by PBMC. In this study, we further investigated whether rBCG-IFN-α could also enhance PBMC cytotoxicity toward
bladder cancer cells.
Materials and methods PBMC were prepared from healthy individuals, left alone or stimulated with rBCG-IFN-α or control MV261 BCG, and used as effector
cells in 51Cr-release assays. Human bladder cancer cell lines T24, J82, 5637, TCCSUP, and UMUC-3 were used as target cells. To determine
the role of secreted rIFN-α as well as endogenously expressed IFN-γ and IL-2 in inducing the cytotoxicity, PBMC were stimulated
with rBCG-IFN-α in the presence of neutralizing antibodies to IFN-α, IFN-γ or IL-2. To determine the role of natural killer
(NK) and CD8+ T cells in inducing the cytotoxicity, both cell types were isolated after BCG stimulation of PBMC and used as effector cells
in 51Cr-release assays.
Results Non-stimulated PBMC showed basal levels of cytotoxicity against all target cell lines tested. MV261 BCG increased the PBMC
cytotoxicity by 1.8- to 4.2-fold. rBCG-IFN-α further increased the PBMC cytotoxicity by up to 2-fold. Elevated production
of IFN-γ and IL-2 by PBMC was observed after rBCG-IFN-α stimulation. Blockage of IFN-α, IFN-γ or IL-2 by neutralizing antibodies
during rBCG-IFN-α stimulation reduced or abolished the induction of PBMC cytotoxicity. Both NK and CD8+ T cells were found to be responsible for the enhanced PBMC cytotoxicity induced by rBCG-IFN-α with the former cell type being
more predominant.
Conclusions rBCG-IFN-α is an improved BCG agent that induces enhanced PBMC cytotoxicity against bladder cancer cells in vitro. This rBCG
strain may serve as an alternative to BCG for the treatment of superficial bladder cancer. 相似文献
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10.
Type I interferon (IFN) signalling, NK cells and NK cell-derived IFN-γ are critical in the early control of genital HSV-2 infection. We have recently reported that NK cells are the source of early IFN-γ in the genital tract in response to HSV-2. However, the response of NK cells to genital HSV-2 infection is not well defined in the context of type I IFN signalling. Here we show that HSV-2 replication was significantly higher in mice deficient in the type I IFN receptor or NK cells compared to wild type controls. There was no detectable IFN-γ production in the genital washes from IFN-α/βR−/− mice or NK cell depleted mice in response to HSV-2 infection compared to control mice. Absence of the type I IFN receptor does not alter homing of NK cells to the genital mucosa. Moreover, the absence of IL-12 had no significant effect on NK cell-derived IFN-γ. Surprisingly, IFN-α/βR−/− mice had more IL-15 positive cells in the genital mucosa in response to HSV-2 infection compared to control mice. We then examined the expression of IL-15 receptors on NK cells. There was no significant differences in the levels of IL-15 receptor expression on NK cells from IFN-α/βR−/− or control mice. Our data clearly suggest that type I IFN receptor signalling is essential for NK cell activation in response to genital HSV-2 infection, and propose that NK cell activation by IL-15 may involve type I IFNs. 相似文献
11.
Walid Abushahba Murugabaskar Balan Ismael Castaneda Yao Yuan Kenneth Reuhl Elizabeth Raveche Andrew de la Torre Ahmed Lasfar Sergei V. Kotenko 《Cancer immunology, immunotherapy : CII》2010,59(7):1059-1071
Hepatocellular carcinoma (HCC) occurs most commonly secondary to cirrhosis due to chronic hepatitis C or B virus (HCV/HBV)
infections. Type I interferon (IFN-α) treatment of chronic HCV/HBV infections reduces the incidence of HCC in cirrhotic patients.
However, IFN-α toxicity limits its tolerability and efficacy highlighting a need for better therapeutic treatments. A recently
discovered type III IFN (IFN-λ) has been shown to possess antiviral properties against HCV and HBV in vitro. In phase I clinical
trials, IFN-λ treatment did not cause significant adverse reactions. Using a gene therapy approach, we compared the antitumor
properties of IFN-α and IFN-λ in a transplantable hepatoma model of HCC. BALB/c mice were inoculated with syngeneic BNL hepatoma
cells, or BNL cells expressing IFN-λ (BNL.IFN-λ cells) or IFN-α (BNL.IFN-α cells). Despite the lack of antiproliferative activity
of IFNs on BNL cells, both BNL.IFN-λ and BNL.IFN-α cells displayed retarded growth kinetics in vivo. Depletion of NK cells
from splenocytes inhibited splenocyte-mediated cytotoxicity, demonstrating that NK cells play a role in IFN-induced antitumor
responses. However, isolated NK cells did not respond directly to IFN-λ. There was also a marked NK cell infiltration in IFN-λ
producing tumors. In addition, IFN-λ and, to a lesser extent, IFN-α enhanced immunocytotoxicity of splenocytes primed with
irradiated BNL cells. Splenocyte cytotoxicity against BNL cells was dependent on IL-12 and IFN-γ, and mediated by dendritic
cells. In contrast to NK cells, isolated from spleen CD11c+ and mPDCA+ dendritic cells responded directly to IFN-λ. The antitumor
activities of IFN-λ against hepatoma, in combination with HCV and HBV antiviral activities warrant further investigation into
the clinical use of IFN-λ to prevent HCC in HCV/HBV-infected cirrhotic patients, as well as to treat liver cancer. 相似文献
12.
Ariyasu T Tanaka T Fujioka N Yanai Y Yamamoto S Yamauchi H Ikegami H Ikeda M Kurimoto M 《In vitro cellular & developmental biology. Animal》2005,41(1-2):50-56
Summary Interferon-alpha (IFN-α) has recently been shown to modulate in vitro T helper (Th) 1-driven responses in the peripheral blood
mononuclear cells (PBMC) of patients with hepatitis B virus or C virus infection. In this study, we examined the in vitro
effects of IFN-α subtypes (IFN-α1, −α2, −α5, −α8, and −α10) on the Th1/Th2 balance in PBMC obtained from patients with hepatitis
virus infection-associated liver disorders and chronic hepatitis (CH), in comparison with the effect on healthy control volunteer
PBMC. The Th1-type cell percentages and Th1/Th2 ratios were significantly higher in the PBMC of patients when compared with
controls both before and after cultivation in vitro, with the IFN-α subtypes. The IFNα-5 induced an increase in the Th2-type
cell percentages in both control and patient PBMC, resulting in that IFN-α5 lowered the Th1/Th2 ratio in patients with CH.
Furthermore, statistical analysis revealed that IFN-α8 significantly promoted an increase in the Th1/Th2 ratios of PBMC from
patients with CH and liver cirrhosis (LC) but not that of PBMC from patients with LC-hepatocellular carcinoma (HCC) and HCC.
These findings imply that hepatitis virus infection and its disease status modify the effects of IFN-α subtypes on Th1 and
Th2 immune balance in patients. Our findings should help to elucidate the mechanisms underlying successful IFN therapy for
hepatitis virus infection and prevention of hepatocellular carcinogenesis. 相似文献
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14.
Sellebjerg F Krakauer M Limborg S Hesse D Lund H Langkilde A Søndergaard HB Sørensen PS 《PloS one》2012,7(6):e35927
Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells), and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26(high) T cells, and the percentage of CD4+CD26(high) T cells that were CD49d(high) correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy. 相似文献
15.
IL-10, IL-13, IFN-γ, tumor necrosis factor (TNF)-α, LT-α, CD154, and TNF-related activation-induced cytokine (TRANCE) were expressed by 2-20% of rheumatoid arthritis (RA) synovial tissue CD4+ memory T cells, whereas CD4+ cells that produced IL-2, IL-4, or IL-6 were not detected. Expression of none of these molecules by individual CD4+ cells correlated with the exception of TRANCE and IL-10, and TRANCE and TNF-α. A correlation between expression of IL-10 and CCR7, LT-α and CCR6, IFN-γ and CCR5, and TRANCE and CXCR4 was also detected. 相似文献
16.
Austin BA Halford WP Williams BR Carr DJ 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(8):5166-5172
An adenoviral (Ad) vector containing the murine IFN-gamma transgene (Ad:IFN-gamma) was evaluated for its capacity to inhibit HSV-1. To measure effectiveness, viral titers were analyzed in cornea and trigeminal ganglia (TG) during acute ocular HSV-1 infection. Ad:IFN-gamma potently suppressed HSV-1 replication in a dose-dependent fashion, requiring IFN-gamma receptor. Moreover, Ad:IFN-gamma was effective when delivered -72 and -24 h before infection as well as 24 h postinfection. Associated with antiviral opposition, TG from Ad:IFN-gamma-transduced mice harbored fewer T cells. Also related to T cell involvement, Ad:IFN-gamma was effective but attenuated in TG from alphabeta TCR-deficient mice. In corneas, alphabeta TCR(+) T cells were obligatory for protection against viral multiplication. Type I IFN involvement amid antiviral efficacy of Ad:IFN-gamma was further investigated because types I and II IFN pathways have synergistic anti-HSV-1 activity. Ad:IFN-gamma inhibited viral reproduction in corneas and TG from alphabeta IFNR-deficient (CD118(-/-)) mice, although viral titers were 2- to 3-fold higher in cornea and TG compared with wild-type mice. The absence of IFN-stimulated antiviral proteins, 2'-5' oligoadenylate synthetase/RNase L, and dsRNA-dependent protein kinase R completely eliminated the antiviral effectiveness of Ad:IFN-gamma. Collectively, the results demonstrate the following: 1) nonexistence of type I IFN receptor does not abolish defense of Ad:IFN-gamma against HSV-1; 2) antiviral pathways oligoadenylate synthetase-RNase L and protein kinase R are mandatory; and 3) alphabeta TCR(+) T cells are compulsory for Ad:IFN-gamma effectiveness against HSV-1 in cornea but not in TG. 相似文献
17.
Toll-like receptor 7 (TLR7) senses viral single-stranded RNA (ssRNA), induces the production of type I interferons (IFNs),
IFN-α and -β, in macrophages such as dendritic cells (DCs), and its immune system protects the host from virus infection.
Here, we found that a crude extract from immature green tea leaves (iTPS) containing a macromolecule with ssRNA fragments,
induces IFN-α production in human macrophage-like cells. In addition IFN-α production was inhibited by treatment with TLR7
inhibitors or a phagocytosis inhibitor. 相似文献
18.
S. Bhattacharyya S. N. Das A. B. Dey K. Nagarkar J. Lobo S. K. Kapoor H. K. Prasad 《Journal of biosciences》1997,22(1):99-109
Interferon-(IFN-γ) has been considered to be a critical protective immunomodulatory component against
Mycobacterium tuberculosis (M. tb.) infection. In this study T-cell proliferation and IFN-γ production upon stimulation with M. tb. were assessed in
patients of pulmonary tuberculosis and healthy contacts. The studies were based on lymphocyte transformation test and detection
of intracellular IFN-γ production by CD4 + ve T-cells by flowcytometry. Patients showed lower levels of proliferation, the
stimulation index being in the range of 2.17 1.1 (mean + SD) compared to the contacts (SI = 4 59±1.6) (P < 0.01). The kinetics
of intracellular induction of IFN-γ on M. tb. stimulation showed a proportional increase in the CD4 + ve T-cell population.
The increase was maximal between 96–120 h of culture. In healthy contacts the number of IFN-γ expressing CD + ve T-cells increased
to 2.5 to 41 × 104 cells/ml in M. tb. stimulated cultures compared to control cultures (0.1 – 15 × 104). In contrast patients showed no/marginal increase in CD4 + ve T-cell population expressing intracellular IFN-γ Thus the
lack of induction of IFN in CD4 + ve T-cells in patients could be a critical shortcoming in their ability to combat tubercle
bacilli infection. 相似文献
19.
M. Baum M. Müller-Steinhardt H. Liesen H. Kirchner 《European journal of applied physiology and occupational physiology》1997,76(2):165-169
The aim of this study was to investigate whether moderate or exhaustive endurance exercise influences cytokine levels in
whole-blood culture supernatants after stimulation. Therefore, eight healthy subjects were first exposed to moderate exercise
on a cycle ergometer for 30 min at 70% of their 4-mmol/l lactic acid (anaerobic) threshold, and 1 week later to exhaustion
(for 90 min) at their anaerobic threshold. Blood samples were taken before, 30 min after and 24 h after each exercise bout.
The following lymphocyte subpopulations were determined: CD14-positive(+)/CD45+, CD4+, CD8+, and CD16+. Cytokine levels in
the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). Production of interleukin (IL)-1β, IL-6 and tumour
necrosis factor (TNF)-α were induced with lipopolysaccharides (LPS), and that of IL-2 and interferon (IFN)-γ with staphylococcal
enterotoxin B (SEB) and phytohaemagglutinin (PHA). Cortisol levels were also determined by ELISA. The lymphocyte subset distribution
was observed to be unchanged after moderate exercise. Thirty minutes after exhaustive exercise, the CD16+ count was found
to be significantly lower, whereas 24 h later the CD4+ count was significantly higher than pre-exercise counts. Moderate exercise
influenced the IFN-γ production (PHA-stimulated), which increased significantly from 974 (391) pg/ml before exercise to 1450 (498) pg/ml
24 h later. Thirty minutes after exhaustive exercise the IFN-γ level in the supernatants (SEB-stimulated) was significantly
decreased (from 14470 (11840) pg/ml before exercise to 6000 (4950) pg/ml after exercise). The IL-1β and TNF-α production per
monocyte was also significantly reduced.
Accepted: 19 February 1997 相似文献
20.
Nishijima K Hisatsune T Kato H Kohyama M Kakehi M Hachimura S Kaminogawa S 《Cytotechnology》1997,25(1-3):89-100
Feeding of a whole casein diet, which abolished the αs1-casein-specific proliferation and IFN-γ productivity of CD4+ T cells, did not affect the proliferative response of CD8+ T cells with regard to the antigen dose response, cell dose response, kinetics of the proliferation and epitope specificity,
as well as IFN-γ production. To assess the characteristics of the CD8+ T cells, we established αs1-casein-specific CD8+ T cell clones from both casein-fed and control mice. The established clones produced different amount of IFN-γ and IL-10,
and one clone derived from the casein-fed mice produced a remarkable amount of IL-10. The clones from casein-fed mice produced
considerable amounts of TGF-β, while those from control mice produced only small amounts. The possible role of CD8+ T cells in oral tolerance is discussed.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献