T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3

Chakir, Habiba; Wang, Haiping; Lefebvre, David E.; Webb, John R.; Scott, Fraser W.

doi:10.1016/s0022-1759(03)00200-x

Cited by 168 publications

(152 citation statements)

References 37 publications

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“…Experiment 1: increased T-bet : Gata3 expression ratio in the MLN of young BBdp rats The T-bet : Gata3 expression ratio of fresh tissue reflects the in vivo Th1/Th2 microenvironment [19]. Therefore, we analysed the expression of T-bet and Gata3 in freshly isolated MLN tissues of BBc and BBdp rats fed an NTP-2000 diet.…”

Section: Resultsmentioning

confidence: 99%

“…At 30 days of age, 1 week after weaning and approximately 5 weeks before diabetes cases begin to appear, the MLN of BBdp rats had a higher T-bet : Gata3 expression ratio than the MLN of BBc rats (p<0.05, n=5 per group; Fig. 1), indicating a predisposition towards a Th1 phenotype (for details refer to [19]). Peyer's patches showed essentially the same pattern (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…Th1/Th2 differentiation involves a balance between Th1-specific T-bet and Th2-specific Gata3 expression [19,41,42]. In the present study, measurement of T-bet and Gata3 expression immediately upon excision of the tissues revealed a decrease in the expression of Gata3 and no change in the expression of T-bet, suggesting that, in vivo, the MLN of young BBdp rats display a Th1 bias that is the result of a Th2 deficit rather than the increased production of the Th1 controller, T-bet.…”

Section: Discussionmentioning

confidence: 99%

“…First, we analysed tissues from NTP-2000-fed rats aged 30 days for expression of the genes encoding T-bet (now known as T-box 21) and GATA binding protein 3 (Gata-3), transcription factors that control Th1 and Th2 cytokine expression [19]. In a second set of experiments, BBc and BBdp rats were fed either the HC or NTP-2000 diet to age 45 days to ensure full Th1 polarisation of naïve T cells [19], and then MLN cells were analysed for the presence of IFN-γ + Th1 cells using intracellular flow cytometry [20]. Both these analyses indicated a Th1 bias in the gut of young, pre-insulitic (NTP-2000-fed) BBdp rats.…”

Section: Methodsmentioning

confidence: 99%

“…PCR products were separated by electrophoresis through a 1.5% agarose gel, and the net band intensity was analysed using a Kodak Image Station 440CF (Eastman Kodak, Rochester, NY, USA). PCR cycle number was optimised as described previously [19]. The absence of genomic DNA contamination was confirmed by performing PCR without reverse transcription amplification of mRNA.…”

Section: Methodsmentioning

confidence: 99%

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Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Chakir¹,

Lefebvre

Wang³

et al. 2005

Diabetologia

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Aims/hypothesis: Type 1 diabetes is the result of an inflammatory T helper 1 (Th1) lymphocyte-mediated beta cell destructive process. The majority of diabetesprone BioBreeding (BBdp) rats fed wheat protein-based diets, such as NTP-2000, develop type 1 diabetes and display a mild coeliac-like enteropathy. Mesenteric lymph nodes (MLNs), which drain the gut, are the major inductive site where dietary antigens are recognised in the gut-associated lymphoid tissue (GALT). We hypothesised that this compartment could be a site of abnormal wheat proteininduced Th1 cell activation. Methods: MLN cells were isolated from BBdp and BB control (BBc) rats that were fed NTP-2000 or a hydrolysed casein (HC)-based diet at ages that pre-date classic insulitis. The inflammatory status, phenotype and proliferation of these cells in response to wheat protein were determined. Results: The expression ratio of T-bet : Gata3, master transcription factors for Th1 and Th2 cytokines, was increased in the MLN from NTP-2000-fed BBdp rats compared with that from BBc rats, mainly due to decreased Gata3 expression. CD3 + CD4 + IFN-γ + T cells were more prevalent in the MLN of wheatfed BBdp rats, but remained at control levels in BBdp rats fed a diabetes-retardant HC diet. BBdp MLN cells proliferated in response to wheat protein antigens in a specific, dose-dependent manner, and >93% of cells were CD3 + CD4 + T cells. This proliferation was associated with a low proportion of CD4 + CD25 + T cells and a high proportion of dendritic cells in the MLN of BBdp rats. Conclusions/ interpretation: Before insulitis is established, the MLNs of wheat-fed BBdp rats contain an unusually high proportion of Th1 cells that proliferate specifically in response to wheat protein antigens.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Chakir¹,

Lefebvre

Wang³

et al. 2005

Diabetologia

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Th1/Th2 Imbalance in Peripheral Blood Echoes Microglia State Dynamics in CNS During TLE Progression

Wang,

Wu,

Chen

et al. 2024

Advanced Science

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Central and systemic inflammation play pivotal roles in epileptogenesis and proepileptogenesis in temporal lobe epilepsy (TLE). The interplay between peripheral CD4+ T cells and central microglia orchestrates the “systemic‐central” immune response in TLE. However, the precise molecular mechanisms linking central and systemic inflammation in TLE remain unknown. This preliminary findings revealed an imbalance in Th1/Th2 subsets in the periphery，accompanied by related cytokines release in TLE patients. they proposed that this peripheral Th1/Th2 imbalance may influence central inflammation by mediating microglial state dynamics within epileptic foci and distant brain regions. In Li‐pilocarpine‐induced TLE rats, a peripheral Th1/Th2 imbalance and observed corresponding central and systemic responses is confirmed. Notably, CD4+ T cells infiltrated through the compromised blood‐brain barrierand are spatially close to microglia around epileptic foci. Intravenous depletion and reinfusion of CD4+ T cells modulated microglia state dynamics and altered neuroinflammatory cytokines secretion. Moreover, mRNA sequencing of the human hippocampus identified Notch1 as a key regulator of Th1/Th2 differentiation, CD4+ T cell recruitment to brain infiltration sites, and the regulation of microglial responses, seizure frequency, and cognition. This study underscores the significance of Th1/Th2 imbalance in modulating the “systemic‐central” response in TLE, highlighting Notch1 as a potential therapeutic target.

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Platycodin D Improves the Immunogenicity of Newcastle Disease Virus‐Based Recombinant Avian Influenza Vaccine in Mice

Xie

Sun

2010

Chemistry & Biodiversity

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The development of an effective influenza vaccine is urgently important for controlling outbreaks of the highly pathogenic avian influenza virus (HPAIV) and reducing the impact of pandemics. The use of an adjuvant in such a vaccine can significantly contribute to improve the immunogenicity. To explore a novel and safe adjuvant for improving the potency of influenza vaccines, platycodin D (1), a saponin from the root of Platycodon grandiflorum, was evaluated for the adjuvant potentials on the specific cellular and humoral immune responses to Newcastle disease virus-based recombinant avian influenza vaccine (rL-H5) in mice. Compound 1 significantly promoted the concanavalin A (Con A)-, the lipopolysaccharide (LPS)-, and the antigen-induced splenocyte proliferation and enhanced the serum antigen-specific IgG, IgG1, IgG2a, and IgG2b antibody titers (P<0.05, P<0.01, or P<0.001) in mice immunized with rL-H5. The mRNA expressions of Th1/Th2 cytokines (IFN-gamma and IL-10) and transcription factors (T-bet and GATA-3) in splenocytes were also markedly up-regulated by 1, compared with the control group immunized with rL-H5 alone (P<0.01 or P<0.001). In addition, 1 remarkably increased the killing activities of natural killer (NK) cells from splenocytes in the immunized mice (P<0.05), which may have important implications for the vaccination against the avian influenza virus. We concluded that 1 could improve the immunogenicity of the rL-H5 vaccine by enhancing both humoral and cellular immune responses in mice, and that 1 is a promising adjuvant for influenza vaccines.

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T-bet/GATA-3 ratio as a measure of the Th1/Th2 cytokine profile in mixed cell populations: predominant role of GATA-3

Cited by 168 publications

References 37 publications

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Th1/Th2 Imbalance in Peripheral Blood Echoes Microglia State Dynamics in CNS During TLE Progression

Platycodin D Improves the Immunogenicity of Newcastle Disease Virus‐Based Recombinant Avian Influenza Vaccine in Mice

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