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1.
Ioanna Marinou Simon H Till David J Moore Anthony G Wilson 《Arthritis research & therapy》2008,10(4):R80
Introduction
A feature of rheumatoid arthritis (RA) is an imbalance between proinflammatory and anti-inflammatory cytokines. Several recent studies have implicated polymorphism in the IL-4 signalling pathway in the development of erosive RA. The aim of the present study was to investigate the role of polymorphism in the IL-4, IL-4Rα and IL-13 genes in RA, including an examination of epistasis. 相似文献2.
Mammalian interleukin-4 (IL-4) and IL-13 are T helper type 2 (Th2) cytokines with pleiotropic functions in immunity. They
signal through receptors containing IL-4Rα and IL-2Rγ or IL-13Rα1. In addition, a decoy receptor, IL-13Rα2, is known to exist
and modulates the function of IL-13. The existence of fish orthologues to mammalian IL-4 and IL-13 is still under debate.
However, the receptor chains have been predicted in zebrafish, and we have previously cloned IL-2Rγ and IL-13Rα2 in rainbow
trout. In this study, we have cloned a further five novel trout IL-4/13 receptors. Thus, each of the IL-4Rα, IL-13Rα1 and
IL-13Rα2 chains has two copies. The identities of the receptors is supported by homology analysis, characteristic domain structure,
phylogenetic tree analysis and synteny analysis in zebrafish. However, the characteristic WSXWS motif of structural importance
in mammalian type I cytokine receptors is missing in all fish IL-4Rα and IL-13Rα1 molecules. All the receptors have a characteristic
domain structure that is similar to their mammalian counterparts except for IL-13Rα1b that has the N-terminal Ig domain missing.
Since this Ig domain is a specific and critical binding unit for IL-13 but not for IL-4 signalling, its absence potentially
converts the IL-13Rα1b into a receptor that can only signal via IL-4 ligation. The existence of duplicated receptor genes
perhaps suggests that more ligands still remain to be discovered that will bind these receptors. The duplicated receptors
are differentially expressed in most tissues and cell lines examined, and their expression can be modulated by LPS, polyIC
and IFN-γ in cell lines. In contrast, the T-cell stimulant phytohaemagglutinin increased the expression of IL-4Rα1 and IL-4Rα2,
but not IL-13Rα1/2, suggesting a role of an IL-4-like molecule in T-cell growth/activation in fish. 相似文献
3.
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
4.
Interleukin (IL)-6, the founding member of IL-6 family cytokines, plays non-redundant roles in hematopoiesis and acute phase
responses. IL-6 signals via a specific private IL-6Rα and a common beta chain gp130. In this study, we have cloned both the
IL-6Rα and gp130 in rainbow trout. The trout gp130 cDNA encodes 906 aa and is similar in size, extracellular domain structure
(D1–D6) and presence of intracellular motifs important for signal transduction to tetrapod gp130s. The trout IL-6Rα cDNA encodes
for 834 aa and is larger compared to tetrapod IL-6Rαs, as are other fish IL-6Rα molecules due to a large D1 domain. However,
the cytokine-binding domain is well conserved across vertebrates, with four conserved cysteine residues in the N-terminal
FNIII domain and a WSXWS motif in the C-terminal FNIII domain. Furthermore, a phylogenetic tree analysis confirmed that the
reported fish IL-6Rα and gp130 molecules are orthologues to their tetrapod counterparts. The extra large D1 domain of the
salmonid IL-6Rα molecules results partially from the insertions of two repetitive sequences of [TS]-[TF]-VSTTT-[ND]-TTSNG
and TTVS-[AT]-IKD-[DG]-S-[KD]-N-[GR], respectively. Furthermore the numbers of repetitions of the two motifs were variable
in different individuals and cell lines, and even in the same fish allelic polymorphism exists. Trout IL-6Rα was expressed
at higher levels than gp130 in a number of tissues examined and the expression of both IL-6Rα and gp130 could be modulated
by LPS and Poly I:C in the cell lines studied. The expression patterns of the receptors suggest that high level expression
of IL-6Rα is critical for IL-6 responsiveness. 相似文献
5.
Interleukin-7 receptor α chain (IL-7Rα)-derived signals are critical for normal T cell development, mature T cell homeostasis,
and longevity of memory T cells. IL-7Rα expression in T cells is dynamically regulated at different developmental and antigen-responding
stages. However, the molecular mechanism underlying the dynamic regulation is not completely understood. Here we describe
generation of a bacterial artificial chromosome (BAC)-based reporter transgenic mouse strain, which contains 210 kb DNA sequence
flanking the Il7r locus. We used in vitro validated EGFP reporter and insulator sequences to facilitate the reporter transgene expression.
Consistent with endogenous IL-7Rα expression, the BAC transgene was expressed in mature T cells, a portion of natural killer
cells but not in mature B cells. In the thymus, the EGFP reporter and endogenous IL-7Rα showed synchronized silencing in CD4+CD8+ double positive stage, were both upregulated in CD4+ or CD8+ single positive thymocytes, and both continued to be co-expressed in na?ve T cells in the periphery. Upon encountering antigen,
the antigen-specific effector CD8+ T cells downregulated both endogenous IL-7Rα and the EGFP reporter, which were upregulated in synchrony in antigen-specific
memory CD8 T cells. These results indicate that the BAC-EGFP transgene reports endogenous IL-7Rα regulation with high fidelity,
and further suggest that the 210 kb sequence flanking the Il7r locus contains sufficient genetic information to regulate its expression changes in T lineage cells. Our approach thus represents
a critical initial step towards systematic dissection of the cis regulatory elements controlling dynamic IL-7Rα regulation during T cell development and cellular immune responses. 相似文献
6.
Michael Kraich Markus Klein Edwin Patiño Henning Harrer Joachim Nickel Walter Sebald Thomas D Mueller 《BMC biology》2006,4(1):13-18
Background
Interleukin 4 (IL-4) is a key regulator of the immune system and an important factor in the development of allergic hypersensitivity. Together with interleukin 13 (IL-13), IL-4 plays an important role in exacerbating allergic and asthmatic symptoms. For signal transduction, both cytokines can utilise the same receptor, consisting of the IL-4Rα and the IL-13Rα1 chain, offering an explanation for their overlapping biological functions. Since both cytokine ligands share only moderate similarity on the amino acid sequence level, molecular recognition of the ligands by both receptor subunits is of great interest. IL-4 and IL-13 are interesting targets for allergy and asthma therapies. Knowledge of the binding mechanism will be important for the generation of either IL-4 or IL-13 specific drugs. 相似文献7.
van Rietschoten JG Smits HH Westland R Verweij CL den Hartog MT Wierenga EA 《Immunogenetics》2000,51(1):30-36
The interleukin-12 receptor (IL-12R) is composed of two subunits, referred to as β1 and β2. Both chains are necessary for
high-affinity IL-12 binding and signalling, although only the IL-12Rβ2 chain contains the intracellular tyrosine residues
responsible for STAT4 activation. This study presents the intron-exon organization of the human IL-12Rβ2-chain gene. Polymerase
chain reaction (PCR) primers designed across the cDNA (U46198) were used to trace introns, by comparing PCR product sizes
obtained using cDNA and genomic DNA as templates. PCR products spanning introns were sequenced to determine the exact splice
sites and flanking regions. The coding region of the gene was found to consist of 15 exons and 14 introns. All intron-exon
boundaries are consistent with the consensus sequence for splice junctions (5′ GT/AG 3′). Comparison of the intron-exon organization
with the human GCSFR gene indicated a remarkably well conserved genomic organization between these two class I cytokine receptors. Interestingly,
we identified an alternatively spliced mRNA, encoding a putative, truncated protein, lacking all signalling potential.
Received: 21 July 1999 / Revised: 2 September 1999 相似文献
8.
Liu H Jacobs BS Liu J Prayson RA Estes ML Barnett GH Barna BP 《Cancer immunology, immunotherapy : CII》2000,49(6):319-324
Many of the actions and receptor components of interleukin-13 (IL-13), a pleiotrophic cytokine with immunotherapeutic potential,
are shared with IL-4. Because human low-grade astrocytoma cells express IL-4 receptors and their growth is arrested by IL-4,
we speculated that IL-13 sensitivity and receptor expression might also be present. The purpose of the current study was to
investigate IL-13 receptor components and sensitivity in a series of glial cell lines derived from adult human non-neoplastic
cerebral cortex, low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Unlike peripheral blood lymphocytes
(PBL), glial cells did not express IL-2 receptor γ chain. IL-13 receptor α-1 (IL-13Rα1), however, was present in 11/13 glial
lines and PBL. Deficient cell lines were all glioblastoma-derived. All anaplastic astrocytoma and glioblastoma but not other
glial lines or PBL expressed IL-13 receptor α-2 (IL-13Rα2). In non-neoplastic glia, low-grade, and anaplastic astrocytoma,
IL-13 decreased DNA synthesis, an effect reversible with antibody to IL-4Rα. Results indicate that low-grade astrocytoma cells
resemble non-neoplastic glia in terms of IL-13 sensitivity and IL-4Rα/IL-13Rα1 receptor profile but alterations occur with
malignant progression. Glioblastoma cells were uniformly insensitive to IL-13 and, unlike other glia, failed to phosphorylate
STAT6 after IL-13 challenge. Data suggest that IL-13 and analysis of IL-13 receptors may have clinical application in glial
tumors.
Received: 23 December 1999 / Accepted: 24 February 2000 相似文献
9.
Nagai Y Nochi T Watanabe K Watanabe K Aso H Kitazawa H Matsuzaki M Ohwada S Yamaguchi T 《Cell and tissue research》2005,322(3):455-462
A pro-inflammatory cytokine, interleukin 18 (IL-18), induces intracellular expression of IL-1 and the release of IL-6. IL-1
and IL-6 has been detected in anterior pituitary cells, suggesting that IL-18 is produced in anterior pituitary cells and
may serve to aid immuno-endocrine regulation. In the present study, we addressed this hypothesis by investigating the intracellular
localization of IL-18 and its receptor in bovine anterior pituitary gland. IL-18 mRNA and its protein were detected in the
anterior pituitary gland by RT-PCR and Western blotting. In situ hybridization showed that IL-18 mRNA was expressed in the
anterior pituitary cells. Immunohistochemistry of IL-18 and specific hormones revealed the presence of IL-18 in somatotrophs.
Furthermore, the expression of GH mRNA in IL-18 immunoreactive cells was confirmed by immuno-laser microdissection. These
results first demonstrated that somatotrophs produced IL-18. Subsequently, the distribution of the IL-18 receptor alpha (IL-18Rα)
was investigated in order to understand IL-18 signaling among the anterior pituitary cells. Bovine IL-18Rα cDNA was partially
sequenced and detected in the anterior pituitary gland by RT-PCR. Immunohistochemistry of IL-18Rα, IL-18 and GH showed that
IL-18Rα was co-localized in IL-18 immunoreactive cells or somatotrophs. These data suggest that IL-18 acts on somatotrophs
as an immuno-endocrine mediator through the autocrine pathway.
This work was supported by a Grant-in-Aid for Scientific Research (B) (No.13460122) from the Ministry of Education, Science
and Culture of Japan 相似文献
10.
Associations of the IL2Rα, IL4Rα, IL10Rα, and IFN
γ
R1 cytokine receptor genes with AIDS progression in a French AIDS cohort 总被引:1,自引:0,他引:1
Do H Vasilescu A Diop G Hirtzig T Coulonges C Labib T Heath SC Spadoni JL Therwath A Lathrop M Matsuda F Zagury JF 《Immunogenetics》2006,58(2-3):89-98
We have performed an extensive analysis of Th1/Th2 cytokine receptors IL2Rα, IL4Rα, IL10Rα, and IFNγR1 gene polymorphisms to evaluate their impact on AIDS progression. The coding regions and promoters of these genes were sequenced in the genetics of resistance to immunodeficiency virus cohort, composed of 327 HIV-1-positive patients with extreme progression phenotypes, slow and rapid progressors, and of 446 healthy control subjects, all of them of Caucasian descent. Overall, 104 single nucleotide polymorphisms and four insertions/deletions with a minor allelic frequency higher than 1% were identified, 21 of them being newly characterized. We observed weak associations for 13 polymorphisms of IL2Rα, IL4Rα, IL10Rα, and IFNγR1, and 11 haplotypes of IL2Rα, IL4Rα, and IFNγR1. However, we could not relate these positive signals to any relevant biological information on the gene function. To affirm these putative associations in AIDS, further confirmation on other AIDS cohorts will be needed. This complete catalog of polymorphisms in IL2Rα, IL4Rα, IL10Rα, and IFNγR1 cytokine receptor genes should also be useful for investigating associations in other immune-related diseases.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
11.
To clarify the response of leptomeningeal cells to immune stimulation, the effect of lipopolysaccharide (LPS) on expression
of IL-6 receptors in the cultured leptomeningeal cells was investigated. The results showed that the expression of IL-6Rα
was invisible in the purified leptomeningeal cells while it was seen in the cells when they were co-cultured with astrocytes.
On the other hand, GP130 was moderately expressed in both conditions. Following incubation with different doses of LPS, IL-6Rα
expression in purified leptomeningeal cells was increased in a time- and dose-dependent manner, while GP130 level remained
unchanged. Concomitantly, phosphorylated ERK1/2 level was increased following LPS stimulation and its inhibition by PD98059
attenuated the LPS-induced increase of IL-6Rα expression. These data indicate that leptomeningeal cells can respond to immunogenic
stimuli as manifested by expression of cytokine receptors. Moreover, ERK1/2 pathway seems to be involved in the process of
LPS-induced IL-6Rα up-regulation in leptomeningeal cells. 相似文献
12.
Lee S Park HH Son HY Ha JH Lee MG Oh TY Sohn DH Jeong TC Lee SH Son JK Lee SG Jun CD Kim SH 《Cell biology and toxicology》2007,23(2):105-112
Mast cell-mediated allergic inflammation is involved in many diseases such as asthma, sinusitis, and rheumatoid arthritis.
Mast cells induce synthesis and production of pro-inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin
(IL)-1β and IL-6 with immune regulatory properties. The formulated ethanol extract of Artemisia asiatica Nakai (DA-9601) has been reported to have antioxidative and anti-inflammatory activities. In this report, we investigated
the effect of DA-9601 on the expression of pro-inflammatory cytokines by the activated human mast cell line HMC-1 and studied
its possible mechanisms of action. DA-9601 dose-dependently decreased the gene expression and production of TNF-α, IL-1β,
and IL-6 on phorbol 12-myristate 13-acetate (PMA)- and calcium ionophore A23187-stimulated HMC-1 cells. In addition, DA-9601
attenuated PMA- and A23187-induced activation of NF-κB as indicated by inhibition of degradation of IκBα, nuclear translocation
of NF-κB, NF-κB/DNA binding, and NF-κB-dependent gene reporter assay. Our in vitro studies provide evidence that DA-9601 might contribute to the treatment of mast cell-derived allergic inflammatory diseases. 相似文献
13.
Xiaoyu Wang Susan V. McLennan Terri J. Allen Stephen M. Twigg 《Journal of cell communication and signaling》2010,4(1):15-23
Connective tissue growth factor (CTGF), also known as CCN2, is implicated in fibrosis through both extracellular matrix (ECM)
induction and inhibition of ECM degradation. The role of CTGF in inflammation in cardiomyocytes is unknown. In some mesenchymal
cell systems, CTGF mediates effects through TGF-β or tyrosine kinase cell surface receptor, TrkA, signalling. In this study,
cellular mechanisms by which CTGF regulates pathways involved in fibrosis and inflammation were explored. Murine H9c2 cardiomyocytes
were treated with recombinant human (rh)CTGF and ECM formation gene expression: fibronectin, collagen type -I and -III and
ECM degradation genes: TIMP-1, TIMP-2 and PAI-1 were found to be induced. CTGF treatment also increased pro-inflammatory cytokines
TNF-α, IL-6, MCP-1 and IL-8. CTGF upregulated TGF-β1 mRNA and rapidly induced phosphorylation of TrkA. The CTGF-induced pro-fibrotic
and pro-inflammatory effects were blocked by anti-TGF-β neutralizing antibody and Alk 5 inhibitor (SB431542). A specific blocker
of TrkA activation, k252a, also abrogated CTGF-induced effects on fibrosis and gene expresison of MCP-1 and IL-8, but not
TNF-α or IL-6. Collectively, this data implicates CTGF in effects on pro-fibrotic genes and pro-inflammatory genes via TGF-β
pathway signalling and partly through TrkA. 相似文献
14.
Ines Cilenšek Amela Hercegovac Jovana Nikolajević Starčević Katarina Vukojević Mirna Saraga Babić Aleksandra Milutinović Živin 《Central European Journal of Biology》2011,6(4):558-564
In diabetic retinopathy (DR) and other angiogenesis-associated diseases, increased levels of cytokines, inflammatory cells,
and angiogenic factors are present. We investigated the hypothesis that rs2243250 polymorphism of the interleukin 4 (IL-4) gene or rs1800896 polymorphism of the interleukin 10 (IL-10) gene, and rs3212227 polymorphism of the 3’ untranslated region (3’ UTR) of the interleukin-12 p40 gene (IL12B) may be associated with the development of proliferative diabetic retinopathy (PDR) in Caucasians with type 2 diabetes (DM2).
This cross sectional case — control study included 189 patients with PDR and 187 patients with type 2 diabetes without PDR.
Polymorphisms rs1800896 of the IL-10 gene, rs2243250 of the IL-4 gene, and rs3212227 of IL12B gene were analyzed by ARMS -PCR and RFLP -PCR methods. Multivariate analysis demonstrated the GG genotype of the rs1800896
polymorphism of the IL-10 gene to be associated with increased risk for PDR (OR=1.99; 95% CI=1.11–3.57; P=0.02), whereas the TT genotype of the rs2243250
polymorphism of the IL-4 gene and the AA genotype of the rs3212227 polymorphism of the IL-12 gene were not independent risk factors for PDR. Our findings suggest that the genetic variations at the IL-10 promoter gene might be a genetic risk factor for PDR in Caucasians with type 2 diabetes. 相似文献
15.
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
16.
Chris P. Verschoor Sameer D. Pant Flavio S. Schenkel Bhawani S. Sharma Niel A. Karrow 《Mammalian genome》2009,20(7):447-454
Altering the balance between pro- and anti-inflammatory responses can influence an animal’s susceptibility to acute or chronic
inflammatory disease; bovine mastitis is no exception. Genetic variation in the form of single nucleotide polymorphisms (SNPs)
may alter the function and expression of genes that regulate inflammation, making them important candidates for defining an
animal’s risk of developing acute or chronic mastitis. The objective of the present study was to identify SNPs in genes that
regulate anti-inflammatory responses and test their association with estimated breeding values (EBVs) for somatic cell score
(SCS), a trait highly correlated with the incidence of mastitis. These genes included bovine interleukin-10 (IL-10) and its
receptor (IL-10R), and transforming growth factor β1 (TGF-β1) and its receptor (TGF-βR). Sequencing-pooled DNA allowed for
the identification of SNPs in IL-10 (n = 2), IL-10Rα (n = 6) and β (n = 2), and TGF-β1 (n = 1). These SNPs were subsequently genotyped in a cohort of Holstein (n = 500), Jersey (n = 83), and Guernsey (n = 50) bulls. Linear regression analysis identified significant SNP effects for IL-10Rα 1185C>T with SCS. Haplotype IL-10Rα
AAT showed a significant effect on increasing SCS compared to the most common haplotype. The results presented here indicate
that SNPs in IL-10Rα may contribute to variation in the SCS of dairy cattle. Although functional studies are necessary to
ascertain whether these SNPs are causal polymorphisms or merely in linkage with the true causal SNP(s), a selection program
incorporating these markers could have a beneficial influence on the average SCS and productivity of a dairy herd. 相似文献
17.
Some studies have shown that IL-18 was associated with aetiology and progression of asthma. However, the association between
single-nucleotide polymorphisms −607C/A (rs1946518) and −137G/C (rs187238) located in the IL-18 gene promoter and asthma risk
was still controversial and ambiguous. To derive a more precise effect on the association between these polymorphisms and
asthma risk, we performed a meta-analysis based on the currently available evidence of the literature. A total of 5 studies
with 1411 cases and 1525 controls for −607C/A polymorphism and 5 studies with 1883 cases and 6645 controls for −137G/C polymorphism
were identified to perform a meta-analysis, up to October 2010. Summary ORs and corresponding 95% CIs for IL-18 polymorphisms
and asthma were estimated using fixed- and random-effects models when appropriate. Heterogeneity and publication bias were
evaluated. We found that individuals carrying AC/CC genotype of −607C/A polymorphism were associated with an increased asthma
risk in recessive model (OR = 1.278; 95% CI, 1.073–1.522). However, no significant association was observed between −137G/C
polymorphism and asthma risk under different contrast models. There was no evidence of publication bias. The present meta-analysis
suggested that IL-18 −607C/A polymorphism in promoter region was associated with asthma risk. 相似文献
18.
Tomohiro Yamaguchi Youichi Suzuki Ryuichi Katakura Takusaburo Ebina Junkichi Yokoyama Yoshiaki Fujimiya 《Cancer immunology, immunotherapy : CII》1998,47(2):97-103
γδT cells play a regulatory role in both primary and metastatic tumor growth in humans. The mechanisms responsible for the
activation and proliferation of circulating γδT cells should be fully understood prior to their adoptive transfer to cancer
patients. We have examined in vitro functional effects of interleukin-15 (IL-15) on highly purified γδT cells isolated from
glioblastoma patients. γδT cells constitutively express the heterotrimeric IL-2 receptor (IL-2R) αβγ, but the levels of IL-2Rβ
or γ expression were not increased by incubation with saturating amounts of IL-15. IL-15 was shown to induce a maximal γδT
cell proliferation, although at much higher concentrations (at least 2000 U/ml) than IL-2 (100 U/ml). Submaximal concentrations
of IL-15 plus low concentrations of IL-2 produced an additive proliferative response. In contrast to the IL-2-induced response,
this activity was completely or partially abrogated by anti-IL-2Rβ, or anti-IL-2Rγ antibodies, but not by anti-IL-2Rα antibodies.
Incubation of γδT cells in the presence of IL-15 resulted not only in the appearance of NK and LAK activity, but also in specific
autologous tumor cell killing activity, an additive effect being seen with IL-15 and IL-2. This IL-15-induced tumor-specific
activity could be significantly blocked by anti-IL-2Rγ and anti-IL-2R-β mAb, but not by anti-IL-2Rα mAb. Thus, in contrast
to IL-2, IL-15 activates tumor-specific γδT cells through the components of IL-2Rβ and IL-2Rγ, but not IL-2Rα. These enhanced
in vitro tumor-specific and proliferative responses of γδT cells seen with IL-15 suggest a rational adjuvant imunotherapeutic
use of γδT cells in cancer patients.
Received: 23 January 1998 / Accepted: 20 May 1998 相似文献
19.
Newborn calves lack a mature immune system. The immune system develops with age, but the role of the expression of cytokine
receptors in the development of immune cells of Peyer’s patches (PPs) in the intestines of calves in the first 2 months has
not yet been elucidated. In this study, the distribution of immune cells and the expression of interleukin (IL) receptors
(R) in the ileal PPs of newborn and 2-month-old calves were investigated immunohistochemically with monoclonal antibodies
against bovine CD4, CD8, IgM, γδTCR, T19, WC3, WC5, and WC6 antigens. The expression of ILRs was examined with antibodies
against CD25 (IL-2Rα), IL-2Rγ, IL-4R, IL-6R, IL-10R, and IL-13R antigens. CD4+, CD8+, γδTCR+, T19+, and WC6+ cells were found to be more widely distributed in the ileal PPs of 2-month-old calves than in those of newborn calves. Moreover,
the expression of CD25 (IL-2Rα), IL-4R, and IL-13R in the ileal PPs of 2-month-old calves was more prominent than that in
newborn calves. These data suggest that the immune system of calves at 2 months of age is developed by reactions to foreign
antigens and aging. 相似文献