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1.
Superiority of the ear pinna over a subcutaneous tumour inoculation site for induction of a Th1-type cytokine response 总被引:1,自引:0,他引:1
This study examines whether a correlation may be found between Th1- or Th2-type cytokine responses and resistance or susceptibility
to tumour growth. Cytokine profiles were investigated in a well-defined mouse tumour model in which the injection site and
the genetic background determine the phenotype of either tumour resistance or tumour susceptibility. DBA/2-derived ESb lymphoma
variant cells with high metastatic capacity were inoculated into syngeneic mice either s.c., where they grow and metastasize,
or into the ear pinna (i.e.), where they do not grow because of induction of protective immunity. Alternatively, the tumour
cells were injected s.c. or i.e. into allogeneic B10.D2 mice, which are resistant to the tumour although they are identical
at the MHC locus. Between 1 and 10 days after tumour cell injection the spleen-derived mRNA was tested for cytokine gene expression
or the spleen cells were analysed by FACScan for T cell activation. The strongest cytokine response was observed in i.e. inoculated
B10.D2 mice. This was characterized by an early (days 2–3) peak of interferon γ (INF-γ), interleukin-2 (IL-2), IL-2 receptor
α (IL-2Rα) and IL-4. The cytokine mRNA response of i.e. inoculated DBA/2 mice was quite similar except that no IFN-γ could
be detected. In s.c. inoculated B10.D2 mice, the IL-2, IL-2Rα and IFN-γ responses were weaker than after i.e. injection while
the IL-4 response was comparable. The most striking difference between these cytokine profiles from tumour-resistant mice
and those of s.c. inoculated tumour-susceptible DBA/2 mice was a delay in the latter in the IL-2, IL-2Rα and IFN-γ responses
and the observation that the IL-4 response was not down-regulated. The persisting IL-4 response could down-regulate a Th1-type
response and thereby explain tumour susceptibility as a consequence of host conditioning.
Received: 4 September 1997 / Accepted: 2 October 1997 相似文献
2.
Lamers CH Langeveld SC Groot-van Ruijven CM Debets R Sleijfer S Gratama JW 《Cancer immunology, immunotherapy : CII》2007,56(12):1875-1883
Background We have treated three patients with carboxy-anhydrase-IX (CAIX) positive metastatic renal cell cancer (RCC) by adoptive transfer
of autologous T-cells that had been gene-transduced to express a single-chain antibody-G250 chimeric receptor [scFv(G250)],
and encountered liver toxicity necessitating adaptation of the treatment protocol. Here, we investigate whether or not the
in vivo activity of the infused scFv(G250)+ T cells is reflected by changes of selected immune parameters measured in peripheral blood.
Methods ScFv(G250)-chimeric receptor-mediated functions of peripheral blood mononuclear cells (PBMC) obtained from three patients
during and after treatment were compared to the same functions of scFv(G250)+ T lymphocytes prior to infusion, and were correlated with plasma cytokine levels.
Results Prior to infusion, scFv(G250)+ T lymphocytes showed in vitro high levels of scFv(G250)-chimeric receptor-mediated functions such as killing of CAIX+ RCC cell lines and cytokine production upon exposure to these cells. High levels of IFN-γ were produced, whilst production
of TNF-α, interleukin-4 (IL-4), IL-5 and IL-10 was variable and to lower levels, and that of IL-2 virtually absent. PBMC taken
from patients during therapy showed lower levels of in vitro scFv(G250)-receptor-mediated functions as compared to pre-infusion,
whilst IFN-γ was the only detectable cytokine upon in vitro PBMC exposure to CAIX. During treatment, plasma levels of IFN-γ
increased only in the patient with the most prominent liver toxicity. IL-5 plasma levels increased transiently during treatment
in all patients, which may have been triggered by the co-administration of IL-2.
Conclusion ScFv(G250)-receptor-mediated functions of the scFv(G250)+ T lymphocytes are, by and large, preserved in vivo upon administration, and may be reflected by fluctuations in plasma IFN-γ
levels. 相似文献
3.
Immunologic significance of HLA class I genes in measles virus-specific IFN-γ and IL-4 cytokine immune responses 总被引:2,自引:0,他引:2
Ovsyannikova IG Ryan JE Vierkant RA Pankratz VS Jacobson RM Poland GA 《Immunogenetics》2005,57(11):828-836
The variability of immune responses modulated by human leukocyte antigen (HLA) genes and secreted cytokines is a significant
factor in the development of a protective effect of measles vaccine. We studied the association between type 1 helper T cells
(Th1)- and Th2-like cytokine immune responses and HLA class I alleles among 339 schoolchildren who previously received two
doses of the measles vaccine. Median values for measles-specific interferon gamma (IFN-γ) and interleukin-4 (IL-4) cytokines
were 40.7 pg/ml [interquartile range (IQR) 8.1–176.7] and 9.7 pg/ml (IQR 2.8–24.3), respectively. Class I HLA-A (*0101 and
*3101) and HLA-Cw (*0303 and *0501) alleles were significantly associated with measles-virus-induced IFN-γ secretion. HLA-A*3101
and Cw*0303 were associated with a higher median IFN-γ response, while A*0101 and Cw*0501 were associated with lower measles-specific
IFN-γ response. We found limited associations between HLA class I gene polymorphisms and Th2-like (IL-4) immune responses
after measles vaccination, indicating that HLA class I molecules may have a limited effect on measles-vaccine-induced IL-4
secretion. Understanding the genetic factors that influence variations in cytokine secretion following measles vaccination
will provide insight into the factors that influence both cell-mediated and humoral immunity to measles. 相似文献
4.
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
5.
Kara E Ozal M Gunay M Kilic M Baltaci AK Mogulkoc R 《Biological trace element research》2011,143(3):1435-1440
The present study aims to examine the effect of zinc supplementation on the release of some cytokines in young wrestlers actively
involved in wrestling. A total of 40 male subjects of the same age group were included in the study: half were wrestlers and
the other half were not involved in sports. The subjects were equally divided into four groups and treated during an 8-week
period as follows: group 1, zinc-supplemented athletes; group 2, non-supplemented athletes; group 3, zinc-supplemented sedentary
subjects, and group 4, non-supplemented sedentary group. Blood samples were taken from each subject at the beginning and at
the end of the study period. The serum tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interpheron-γ levels (IFN-γ)
were determined using the enzyme-linked immunosorbent assay method. At the beginning of the study, there were no significant
differences of the measured parameters between the four study groups. At the end of the study, the levels of TNF-α, IL-2,
and IFN-γ were significantly higher in the two zinc-supplemented groups compared to those that did not receive supplementation,
regardless of the activity status (p < 0.01). 相似文献
6.
To determine some early signs connected with the increased risk of future allergy development, gene expression and production
of selected cytokines were tested in children of allergic mothers and compared with newborns of healthy mothers. Expression
of IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, TNF-α, TGF-β and EGF was tested in cord blood cells using real-time PCR and
production of these cytokines was evaluated in cord sera by ELISA. Gene expression of IL-2, IL-4, IL-8, IFN-γ, IL-1β, TNF-α
and TGF-β was decreased and that of IL-10, IL-13 and EGF increased in children of allergic mothers in comparison with those
of healthy mothers. Significant differences in sera of healthy and allergic groups were only in IL-10 and EGF. Different relationship
among serum cytokine levels reflects the fact that the cytokines are not produced only by blood cells. Significantly decreased
production of EGF in newborns of allergic mothers could negatively influence maturation of mucosal membranes of these children
and support thus their easier allergization. Allergic phenotype pointing to the bias to TH2 response and to possibly impaired intestine maturation was apparent already on the level of cord blood and could serve as
a predictive sign of increased allergy risk. 相似文献
7.
Yusuke Nakanishi Akira Hosono Yasuhiro Hiramatsu Teiji Kimura Ryo Nakamura Shuichi Kaminogawa 《Cytotechnology》2005,47(1-3):69-77
We demonstrate immunomodulatory effects, especially those involving murine intestinal IgA secretion, in Peyer's patch cells
following oral administration of Bifidobacterium immunomodulator (BIM) derived from sonicated B. pseudocatenulatum 7041. BALB/c mice were administered BIM orally for 7 consecutive days. The PP cells demonstrated upregulated secretion of
total IgA including BIM-specific IgA following BIM administration. In observing the response of PP cells co-cultured with
BIM, we found enhanced secretion of interferon-γ (IFN-γ) and interleukin (IL)-6 in the CD4+ T cells. In contrast, IL-12 secretion by Thy1.2− PP cells was enhanced, but secretion of IFN-γ, IL-5, and IL-6 was not significantly affected. Furthermore, the population
of CD4+ CD45RBhigh T cells in PP increased following oral administration of BIM. These data suggest that CD4+ T cells were affected by BIM administration. Overall, the results show that oral administration of BIM induced CD4+ PP cells to change their expression of cell surface antigen and cytokine production. 相似文献
8.
T cell clones (CD4+CD8–TCRαβ+γδ–) derived from bone marrow transplant recipients were stimulated with phytohaemagglutinin (PHA) +interleukin-2 (IL-2) in the
presence of irradiated (50 Gy) peripheral blood mononuclear cells (PBMC) derived from acute leukaemia patients(leukaemic PBMC
containing more than 95% blast cells). Leukaemic PBMC could function as accessory cells during mitogenic T cell activation
resulting in both T cell proliferation and a broad T cell cytokine response [IL-3, IL-4, IL-10, granulocyte/macrophage-colony-stimulating
factor (GM-CSF) tumour necrosis factor α (TNFα) and interferon γ (IFNγ) secretion]. Blockade of IL-1 effects by adding IL-1
receptor antagonist together with PHA+IL-2+leukaemia blasts increased T cell proliferation, whereas IL-6-neutralizing antibodies
did not alter T cell proliferation. A qualitatively similar T cell cytokine response and a similar cytokine profile (highest
levels detected for GM-CSF and IFNγ) were detected when normal polyclonal T cell lines were stimulated with PHA in the presence
of non-irradiated leukaemic PBMC. When leukaemic PBMC derived from 18 acute myelogenous leukaemia patients were cultured with
PHA and cells from a polyclonal T cell line, increased concentrations of the T cell cytokines IFNγ and IL-4 were detected
for all patients. We conclude that T cell activation resulting in proliferation and a broad cytokine response can take place
in the presence of excess acute myelogenous leukaemia blasts.
Received: 30 November 1995 / Accepted: 9 January 1996 相似文献
9.
In this study, we report on the interferon-γ (IFN-γ) and interleukin-4 (IL-4) cytokine responses to phorbol myristate acetate
(PMA)+ionomycin-stimulated CD3+ lymphocytes in asthmatic subjects when compared with normal donors. There was a significantly
lower production of intracellular IFN-γ in asthmatic patients. No difference was found for IL-4 production between these two
groups.
After administration of a multivitamin-mineral supplement containing selenium, zinc, vitamin A, vitamin B6, vitamin C, and vitamin E for 6 mo, a significant increase in the percentage of CD3+/IL-4 positive cells (p<0.05) was found.
The induction of endothelial cell adhesion molecule (CAM) expression in cultured human umbilical vein endothelial cells (HUVEC)
and whole-blood mixture was studied using flow cytometry. The ICAM-1 and VCAM-1 expressions were higher in the patients than
in control donors (p<0.05). There is a correlation between the increased percentage of CD3+/IFN-γ positive cells and reduced endothelial ICAM-1
and VCAM-1 expression after 6 mo of intervention period. No apparent effect of supplementation on CAM expression was found,
suggesting that these changes do not arise from an antioxidant mechanism. This newly developed whole-blood technique for the
assessment of CAM expression can be of use for monitoring therapy in inflammatory diseases. 相似文献
10.
Miao Yin Liang Zhang Xiao-ming Sun Liu-feng Mao Jie Pan 《Molecular biology reports》2010,37(4):2049-2054
To investigate the effect of apolipoprotein E (apoE) on cytokine expression profile of the liver of young mice, quantitative
RT-PCR (qRT-PCR) assay and cytokine antibody array for multiplex analysis of 62 cytokines have been used to analyze characteristics
of expression of cytokines in the liver of 6-week-old apoE-null (apoE−/−) mice. The levels of plasma cytokines were also analyzed. The mRNA level of IL-1β, IL-2, IL-6, ICAM-1, VCAM-1, MCP-1, NF-κB
(p65), IFN-γ and IκB-α were increased significantly in apoE−/− mice comparative to wild-type (WT) mice. IL-4, IL-10 and GM-CSF, however, were slightly decreased. Compared with WT, levels
of 21 cytokines altered twofold or more in apoE−/− mice, including 10 cytokines increased and 11 decreased. Expression patterns of IL-1β, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ
and VCAM-1 showed identical trend between cytokine antibody array and qRT-PCR analysis. Moreover, levels of IL-1β, IFN-γ and
IL-6 in the plasma were elevated, while IL-4 was lightly decreased in apoE−/− mice compared to those in WT mice. These results implied that promotion of type I immune response in the liver of young apoE−/− mice due to alteration of these cytokines, and the phenotypes may be caused by the regulation of NF-κB. The inflammation
and lipid metabolism dysfunction in the liver cooperated in dysfunction of the liver in young apoE−/− mice. 相似文献
11.
Inflamed synovium of rheumatoid arthritis (RA) has been associated with a T helper (Th)1 cytokine profile but the blood situation
remains to be clarified. We studied the differential IFN-γ producing activity of peripheral blood mononuclear cells (PBMCs)
from RA patients (RA-PBMCs) and from healthy controls (H-PBMCs) in response to IL-12 and IL-18. RA-PBMCs had a decreased IFN-γ
production in response to IL-12 and IL-18 when compared with H-PBMCs. RA-PBMCs activated with phytohemagglutinin and phorbol
12-myristate 13-acetate showed an increased sensitivity to IL-12 and IL-18, but still the RA-PBMC response was lower. IL-18
increased IL-12-stimulated IFN-γ production from RA synovium cells obtained after collagenase digestion more effectively than
that of RA- or H-PBMCs. A specific inhibitor of IL-18 bioactivity, IL-18-binding protein (IL-18BP), down-regulated IL-12-induced
IFN-γ production by RA- or H-PBMCs and had a remarkable effect on RA synovium cells. In conclusion, RA disease combines a
polarized immune response with an active Th1 in inflamed joints and a reduced Th1 pattern in peripheral circulation. 相似文献
12.
It has been reported that interferon-γ (IFN-γ) facilitates differentiation of PC-12 cells and murine adult neural stem cells.
Here we show that IFN-γ promotes the differentiation of C17.2 neural progenitor cells (NPC) into a neuronal phenotype characterized
by neurite outgrowth and the expression of the neuronal marker protein β-III tubulin. IFN-γ induced an increase in the activity
c-jun N-terminal kinase (JNK) without affecting activities of extracellular signal-regulated kinases (ERKs 1 and 2). An inhibitor
of JNK blocked the ability of IFN-γ to promote differentiation of NPC into neurons, whereas an inhibitor of ERKs 1 and 2 did
not. Our findings show that the pro-inflammatory cytokine, IFN-γ has the potential to stimulate neurogenesis, suggesting roles
for this cytokine in development and repair of the nervous system. 相似文献
13.
T-cell responses to antigens are classified on the basis of the cytokines they produce as either Th1 (IFN-γ, IL-2) or Th2 (IL-4, IL-10), with these Th types being indicative of either cell-mediated or antibody-mediated responses, respectively. Using this classification, T-cell responses in MHC-class-II-restricted autoimmune diseases appear to be predominantly of the Th1 type, based on the presence of high levels of IFN-γ. This simplistic classification has recently been challenged, however, as disease incidence and severity are frequently elevated in animals that have a deficient IFN-γ response. The recent data discussed here indicate that the cytokine circuits involved in the regulation of cell-mediated and humoral immune responses during the development of autoimmune arthritis are more complex than originally proposed; perhaps our characterization of autoimmune responses as strictly Th1 or Th2 is overly simplistic, especially as it pertains to the role of IFN-γ. 相似文献
14.
Gutiérrez-Ortega A Sandoval-Montes C de Olivera-Flores TJ Santos-Argumedo L Gómez-Lim MA 《Transgenic research》2005,14(6):877-885
Transgenic plants have been employed successfully as a low-cost system for the production of therapeutically valuable proteins,
including antibodies, antigens and hormones. Here, we report the expression of a cytokine with immunomodulatory function,
mouse interleukin-12 (IL-12), in transgenic tomato plants. Single-chain mouse IL-12 driven by the CaMV 35S promoter, accumulates
to high levels in leaves and fruits (up to 7.3 and 3.4 μg per gram of fresh weight, respectively). Mouse IL-12 expressed in
tomato displays biological activity in vitro, as determined by interferon-γ (IFN-γ) secretion by T cells. Possible uses of this plant-based cytokine involving mucosal
delivery are discussed 相似文献
15.
Saya Kuribayashi Yoshihiro Sakoda Takeshi Kawasaki Tomohisa Tanaka Naoki Yamamoto Masatoshi Okamatsu Norikazu Isoda Yoshimi Tsuda Yuji Sunden Takashi Umemura Noriko Nakajima Hideki Hasegawa Hiroshi Kida 《PloS one》2013,8(7)
Highly pathogenic avian influenza viruses (HPAIVs) cause lethal infection in chickens. Severe cases of HPAIV infections have been also reported in mammals, including humans. In both mammals and birds, the relationship between host cytokine response to the infection with HPAIVs and lethal outcome has not been well understood. In the present study, the highly pathogenic avian influenza viruses A/turkey/Italy/4580/1999 (H7N1) (Ty/Italy) and A/chicken/Netherlands/2586/2003 (H7N7) (Ck/NL) and the low pathogenic avian influenza virus (LPAIV) A/chicken/Ibaraki/1/2005 (H5N2) (Ck/Ibaraki) were intranasally inoculated into chickens. Ty/Italy replicated more extensively than Ck/NL in systemic tissues of the chickens, especially in the brain, and induced excessive mRNA expression of inflammatory and antiviral cytokines (IFN-γ, IL-1β, IL-6, and IFN-α) in proportion to its proliferation. Using in situ hybridization, IL-6 mRNA was detected mainly in microglial nodules in the brain of the chickens infected with Ty/Italy. Capillary leakage assessed by Evans blue staining was observed in multiple organs, especially in the brains of the chickens infected with Ty/Italy, and was not observed in those infected with Ck/NL. In contrast, LPAIV caused only local infection in the chickens, with neither apparent cytokine expression nor capillary leakage in any tissue of the chickens. The present results indicate that an excessive cytokine response is induced by rapid and extensive proliferation of HPAIV and causes fatal multiple organ failure in chickens. 相似文献
16.
The focal adhesion kinase (FAK) family kinases, including FAK and proline-rich kinase 2 (Pyk)2, are the predominant mediators
of integrin αvβ3 signaling events that play an important role in cell adhesion, osteoclast pathology, and angiogenesis, all
processes important in rheumatoid arthritis (RA). Using immunohistochemical and western blot analysis, we studied the distribution
of phospho (p)FAK, pPyk2, pSrc, pPaxillin and pPLCγ in the synovial tissue (ST) from patients with RA, osteoarthritis (OA)
and normal donors (NDs) as well as in RA ST fibroblasts and peripheral blood differentiated macrophages (PB MΦs) treated with
tumor necrosis factor-α (TNFα) or interleukin-1β (IL1β). RA and OA STs showed a greater percentage of pFAK on lining cells
and MΦs compared with ND ST. RA ST fibroblasts expressed pFAK at baseline, which increased with TNFα or IL1β stimulation.
Pyk2 and Src were phosphorylated more on RA versus OA and ND lining cells and MΦs. pPyk2 was expressed on RA ST fibrobasts
but not in MΦs at baseline, however it was upregulated upon TNFα or IL1β activation in both cell types. pSrc was expressed
in RA ST fibroblasts and MΦs at baseline and was further increased by TNFα or IL1β stimulation. pPaxillin and pPLCγ were upregulated
in RA versus OA and ND lining cells and sublining MΦs. Activation of the FAK family signaling cascade on RA and OA lining
cells may be responsible for cell adhesion and migration into the diseased STs. Therapies targeting this novel signaling pathway
may be beneficial in RA. 相似文献
17.
Hasem Habelhah Futoshi Okada Kazumoto Nakai Sung Ki Choi Jun-ichi Hamada Masanobu Kobayashi M. Hosokawa 《Cancer immunology, immunotherapy : CII》1998,46(6):338-344
Previously we reported the malignant progression of QR-32, a regressor-type tumor clone, following co-implantation with foreign
bodies (gelatin sponge or plastic plate) in normal syngeneic C57BL/6 mice. We also reported that the progression of QR-32
cells by a gelatin sponge was significantly inhibited in the mice administered polysaccharide K (PSK) and that PSK induced
an increase of radical scavengers, especially manganese superoxide dismutase (Mn-SOD), locally at the site of tumor tissues.
In this study, to reveal the possible mechanism by which PSK induced Mn-SOD in the tumor tissues, we examined the mRNA expression
and protein levels of inflammatory cytokines in the tissues. We found that mRNAs of tumor necrosis factor α (TNFα) and interleukin-1α
(IL-1α) were considerably expressed in both PSK-treated and phosphate-buffered-saline-treated tumors, and that the mRNA expression
and protein level of interferon γ (IFNγ) increased in the tumor tissues treated with PSK. In vitro treatment of QR-32 cells
with IFNγ did not significantly increase the production of Mn-SOD; however, the combination of IFNγ with TNFα increased the
Mn-SOD production more effectively than did any of the cytokines used singly. Furthermore, we observed the down-regulation
of the mRNA expression and protein level of transforming growth factor β (TGFβ) in the tumor tissues treated with PSK, and
that in vitro treatment of QR-32 cells with TGFβ decreased the production of Mn-SOD. These results suggest that PSK suppresses
the progression of QR-32 cells by increasing Mn-SOD via the modulation of inflammatory cytokines; that is, by decreasing TGF-β
and increasing IFN-γ.
Received: 7 October 1997 / Accepted: 31 March 1998 相似文献
18.
Daneshmandi S Pourfathollah AA Pourpak Z Heidarnazhad H Kalvanagh PA 《Molecular biology reports》2012,39(2):1845-1853
Asthma is a multifactor inflammatory disorder, and its management requires understanding of its various pathogenesis and control
mechanisms. Cytokines and other inflammatory mediators are important factors in asthma pathophysiology. In this study, we
evaluated the role of cytokine polymorphisms in the asthma susceptibility, progress, control, and lung functions. IL-4-C590T
polymorphism by PCR-RFLP method, IFN-γ T+874A, TNF-α-A308G, IL-6 G−174C and TGF-β T+869C variants by ARMS-PCR method and IgE
serum level by ELISA technique were determined in 81 asthmatic patients and 124 normal subjects. Asthma diagnosis, treatment
and control levels were considered using standard schemes and criteria. TNF-α−308GA genotype was more frequent in asthmatics
(P = 0.025, OR 3.352), and polymorphisms between different asthma control levels (P > 0.05) were not different. IFN-γ+874AT genotype had a positive correlation with the familial history of asthma (P = 0.034, OR 2.688). IL-6−174C allele (P = 0.045), TNF-α−308GG genotype (P = 0.002) and TNF-α−308G allele (P = 0.004) showed reduced values, and TNF-α−308GA genotype (P = 0.002) increased FEF25-75 value in asthmatics. IFN-γ+874AA genotype caused a decrease in FVC factor (P = 0.045). This study showed that TNF-α−308GA is a risk factor for asthma, but cytokine gene variants do not affect asthma
control and IgE serum levels. Variants producing lower levels of IL-6, TNF-α and IFN-γ are associated with reduced pulmonary
capacities. To achieve an appropriate schema for asthma management, further studies with consideration of different aspects
in a larger group of patients would be more elucidative. 相似文献
19.
Gabriella Par Laszlo Szereday Timea Berki Laszlo Palinkas Melinda Halasz Attila Miseta Geza Hegedus Julia Szekeres-Bartho Aron Vincze Bela Hunyady Alajos Par 《PloS one》2013,8(7)
Background
Chronic hepatitis C (CHC) patients achieving rapid virological response (RVR) on PEG-IFN/ribavirin (P/R) therapy have high chance of sustained virological response (SVR). To analyze host immunological factors associated with RVR, viral kinetics, phenotype distribution and Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) were studied prior to and during P/R therapy.Methods
TNF-α, IFN-γ, IL-2, IL-6, IL-4 and IL-10 production by PBMC were measured after Toll-like receptor 4 (TLR-4) or phorbol myristate acetate/Ionomycin stimulation in 20 healthy controls and in 50 CHC patients before receiving and during P/R therapy. RVR was achieved by 14, complete early virological response (cEVR) by 19 patients and 17 patients were null-responders (NR).Results
Patients with RVR showed an increased baseline TNF-α and IL-6 production by TLR-4 activated monocytes and increased IFN-γ, decreased IL-4 and IL-10 production by lymphocytes compared to non-RVR patients. SVR was also associated with increased baseline TNF-α production and decreased IL-10 levels compared to patients who did not achieve SVR. Baseline IL-2 production was higher in cEVR compared to NR patients. Antiviral treatment increased TNF-α, IL-6 production by monocytes and IFN-γ secretion by lymphocytes and decreased IL-4 and IL-10 production by lymphocytes in cEVR compared to NR patients.Conclusion
RVR was associated with increased baseline proinflammatory cytokine production by TLR-4 stimulated monocytes and by activated lymphocytes. In null-responders and in patients who did not achieve SVR both TLR-4 sensing function and proinflammatory cytokine production were impaired, suggesting that modulation of TLR activity and controlled induction of inflammatory cytokine production may provide further therapeutic strategy for CHC patients non-responding to P/R treatment. 相似文献20.
Margaret R. Dunne Laura Madrigal-Estebas Laura M. Tobin Derek G. Doherty 《Cancer immunology, immunotherapy : CII》2010,59(7):1109-1120
Vγ9Vδ2 T cells respond to pyrophosphate antigens and display potent antitumour activity in vitro. We have investigated the
potential of the most potent phosphoantigen known to activate Vγ9Vδ2 T cells, (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate (HMB-PP), as an adjuvant for dendritic cell (DC)-based vaccines. A single stimulation
of peripheral blood mononuclear cells with HMB-PP and IL-2 was sufficient to generate lines of effector memory Vγ9Vδ2 T cells
that retained their cytolytic and cytokine secretion activities. These cells induced differentiation of DC into semi-mature
antigen-presenting cells expressing CD86, CD11c, CD54, HLA-DR, CD83 and CD40, which secreted low levels of bioactive IL-12
but no IL-10. Vγ9Vδ2 T cells also strongly costimulated IL-12 release but inhibited IL-10 production by lipopolysaccharide
(LPS)-stimulated DC. When substituted for Vγ9Vδ2 T cells, IFN-γ did not induce full DC maturation but it augmented IL-12 and
inhibited IL-10 release by LPS-stimulated DC, in a manner similar to HMB-PP-activated Vγ9Vδ2 T cells. Our findings indicate
that Vγ9Vδ2 T cells, stimulated with nanomolar concentrations of HMB-PP, strongly promote T helper type 1 (Th1) responses
through their ability to induce DC maturation and IL-12 secretion. This adjuvant activity may prove useful in DC-based cancer
therapies. 相似文献