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Th1/Th2 Balance (th1/th2 + balance)
Selected AbstractsNKT cells are dispensable in the induction of oral tolerance but are indispensable in the abrogation of oral tolerance by prostaglandin EEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 1 2003Ryotaro Ishimitsu Abstract NK1.1+ ,,, T cells (NKT cells) regulate the Th1/Th2 balance in response to dietary Ag, which may be involved in regulation of oral tolerance. OVA-specific IgE and IgG1 Ab levels were significantly lower following an i.p. injection of OVA (in CFA) in C57BL/6 mice orally given a single, high dose (25,mg) of OVA than in those orally given PBS. The oral tolerance was normally induced in J,281,/, mice which lack V,14+ NKT cells, suggesting that NKT cells are dispensable for induction of oral tolerance. Treatment with PGE1 or PGE2 abrogated the oral tolerance in J,281+/+ mice; this abrogation was accompanied by an OVA-specific Th2-dominant response. The abrogation of oral tolerance by PGE1 was not evident in J,281,/, mice. Treatment with PGE1 induced an early increase in IL-4 production by liver NKT cells in normal mice and neutralization of the early IL-4 by administration of anti-IL-4 mAb abolished PGE1 -induced abrogation of oral tolerance. These results suggest that liver NKT cells producing IL-4 are responsible for the down-regulation of oral tolerance that is caused by the PGE molecules. [source] Alteration of CXCR4 expression and Th1/Th2 balance of peripheral CD4-positive T cells can be a biomarker for leukocytapheresis therapy for patients with refractory ulcerative colitisINFLAMMATORY BOWEL DISEASES, Issue 7 2009Hiroshi Nakase MD No abstract is available for this article. [source] ORIGINAL ARTICLE: Imbalance of T-cell Transcription Factors Contributes to the Th1 Type Immunity Predominant in Pre-eclampsiaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 1 2010Zhou Jianjun Problem, Extensive studies have demonstrated that Th1 type immunity is predominant in pre-eclampsia, but there is little concern with regard to the intracellular mechanisms behind this initial T-cell polarization. In this study, we investigated whether the imbalance of the T-cell transcription factors contributes to it. Method of study, A total of 15 pre-eclamptic patients and 15 healthy pregnant women were enrolled in this study. The expression levels of transcription factors for Th1 (T-bet), Th2 (GATA3), Th17 (RORc) and Treg (FOXP3) cells, together with the Th1/Th2 status, were simultaneously investigated in both peripheral blood mononuclear cells (PBMCs) and decidua. Results, The expression levels of FOXP3 mRNA were decreased in both PBMCs and decidua from pre-eclamptic patients compared with healthy pregnant women (P < 0.05), and T-bet mRNA and RORc mRNA were significantly increased (P < 0.05), while Th1/Th2 balance shifted toward the Th1 immunity. Furthermore, there was a negative correlation between FOXP3 mRNA and Th1 cells (P < 0.05), and the expression level of T-bet mRNA correlated strongly with Th1 cells (P < 0.05). Conclusion, Decreased expression of FOXP3 mRNA and increased expression of T-bet mRNA may contribute to Th1 type immunity predominant in pre-eclampsia. [source] Polymorphisms in TBX21 and STAT4 increase the risk of systemic sclerosis: Evidence of possible gene,gene interaction and alterations in Th1/Th2 cytokinesARTHRITIS & RHEUMATISM, Issue 12 2009Pravitt Gourh Objective Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs. Dysregulation of the immune system, including the Th1/Th2 cytokine balance, is central to the pathogenesis of SSc. This study was undertaken to investigate the hypothesis that single-nucleotide polymorphisms (SNPs) in TBX21 and STAT4, both of which are critical transcription factors that regulate the Th1/Th2 balance, are associated with SSc susceptibility. Methods We tested SNPs in TBX21 and STAT4 for association with SSc in 2 independent cohorts, the SSc Registry cohort (880 SSc cases and 507 controls) and the University of Texas SSc cohort (522 cases and 531 controls). Additional white control genotypes were obtained from public repositories. We also investigated for gene,gene interactions. Plasma cytokines and whole blood gene expression profiles were examined to determine functional effects of these SNPs. Results Multiple SNPs in TBX21 and STAT4 were found to be associated with SSc. In a combined analysis of 902 SSc patients and 4,745 controls, TT genotyping of the TBX21 rs11650354 variant revealed a recessive pattern for disease susceptibility (Pcorr = 1.4 × 10,15, odds ratio 3.37, 95% confidence interval 2.4,4.6). In an analysis of 1,039 SSc patients and 3,322 controls, the A allele of the STAT4 variant rs11889341 was associated with increased SSc susceptibility in a dominant pattern (Pcorr = 2.4 × 10,5, odds ratio 1.29, 95% confidence interval 1.2,1.5). Furthermore, we identified gene,gene interaction among the TBX21 and STAT4 variants, such that the STAT4 genotype increased the risk of SSc only in the TBX21 CC genotype group. SSc patients carrying the TBX21 CC genotype had higher interleukin-6 (IL-6) and tumor necrosis factor , levels, and those with the TT genotype had elevated IL-2, IL-5, IL-4, and IL-13 (Th2) levels, compared with controls. Whole blood expression profiles revealed dysregulation of type I interferon pathways in the CC group and T cell pathways in the TT group of the TBX21 SNP. Conclusion The present results, from studies of 2 independent cohorts, indicate that SNPs in TBX21 and STAT4 contribute uniquely and interactively to SSc susceptibility, leading to altered cytokine balance and immune dysregulation. [source] Association of neuropeptides with Th1/Th2 balance and allergic sensitization in childrenCLINICAL & EXPERIMENTAL ALLERGY, Issue 11 2006G. Herberth Summary Background Among neurogenic factors, the neuropeptides have an important regulatory influence on immune system activity and may lead to allergic sensitization. Objective The aim of our study was to investigate the relationship of the neuropeptides vasoactive intestinal peptide (VIP), somatostatin (SOM) and substance P (SP) on modulation of Th1/Th2 balance and allergic sensitization in children. Methods Within the LISAplus (Life style,Immune system,Allergy) study, blood samples of 321 six-year-old children were analysed for concentration of neuropeptides, Th1 and Th2 cytokines, transcription factors for T cell regulation and suppressors of cytokine signalling. In addition, samples were screened for specific IgE against inhalant and food allergens. Results Children with high SOM values showed a Th2 polarization and a reduced expression of FOXP3, the marker for regulatory T cells. High (VIP) levels correlated inversely with the expression of T cell transcription factors (Tbet and SOCS3). In contrast, elevated levels of SP were associated with reduced GATA3 and SOCS3 expression and with increased IFN-, concentrations. Allergic sensitization was more prevalent in children with higher SOM and VIP concentrations but not associated with SP levels. Conclusion Our data reveal an association between neuropeptides and modulatory effects on immune cells in vivo, especially on Th1/Th2 balance with a correlation to allergic sensitization in children. We suggest that elevated SOM and VIP concentrations and the inducing factors should be considered as allergy risk factors. [source] Association study of 15 novel single-nucleotide polymorphisms of the T-bet locus among Finnish asthma familiesCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2004E. Ylikoski Summary Objective T-box expressed in T cells (T-bet) is a transcription factor regulating the commitment of T helper (Th) cells by driving the cells into the Th1 direction. Abnormal Th1/Th2 balance may lead to complex disorders like asthma or autoimmune diseases. Recent studies have suggested that T-bet might be a candidate gene for asthma. This led us to screen 23 Finnish individuals for single-nucleotide polymorphisms (SNPs) in the T-bet locus and study the association between the SNPs and high serum IgE level and asthma. Methods We screened all six exons, adjacent intronic areas and 2 kb of the 5,-flanking region from 23 individuals utilizing WAVEÔ technology. To explore whether T-bet is associated in serum IgE regulation or asthma we genotyped the SNPs in a Finnish asthmatic founder population. The association analyses were made using haplotype pattern mining. Results Fifteen novel SNPs were found in the T-bet gene. Within the Finnish asthmatic founder population, there was no association between T-bet SNPs and high serum IgE level or asthma. Conclusions The genetic variability in the T-bet gene does not play a role in the pathogenesis of human asthma. Our results provide a novel panel of SNPs in T-bet and will help determine whether the SNPs have a functional role in other T cell-mediated diseases. [source] Dietary nucleic acids promote a shift in Th1/Th2 balance toward Th1-dominant immunityCLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2000Sudo Background Dietary sources of nucleic acids and their relative components are known to affect host immune function; however, it has not yet been clarified whether such dietary nucleic acids influence the pathogenesis of allergic reaction. Objective The purpose of this study is to elucidate the effect of dietary nucleic acids on Th1/Th2 balance. Methods Both human flora-associated and specific pathogen-free BALB/c mice were maintained on either nucleic acid-free, or -supplemented diets. The effects of nucleic acids on both in vivo antibody levels and in vitro splenocyte cytokine production were compared using these mice. Results Supplementation of nucleic acids caused a reduction in the serum antibody levels of total IgM, IgG, IgG1, and IgE in the human flora-associated mice without affecting the composition of intestinal flora. In contrast, there was no significant difference of the serum IgG2a levels between nucleic acid-free and -supplemented mice. Such a phenomenon as that, the supplementation of dietary nucleic acids reduces the serum IgE or IgG1 levels, but not the IgG2a level, was also seen in the specific pathogen free mice. Moreover, when the mice were systematically challenged with ovalbumin, the supplementation of nucleic acids also suppressed the serum ovalbumin-specific IgE and IgG1 antibody levels as well as in vitro IL-4 and IL-10 secretion, while enhancing both the serum ovalbumin-specific IgG2a antibody levels and in vitro IFN , secretion. Conclusion These results suggested that dietary nucleic acids may play an important role in promoting a shift in Th1/Th2 balance toward Th1-dominant immunity. [source] | ||||||||||