Systemic inflammation drives rapid conversion of conventional CD4+ T cells to Treg in vivo
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ABSTRACT:
PROVIDER: PRJNA417240 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6260510.fastq.gz | Fastqsanger.gz | |||
| SRR6260520.fastq.gz | Fastqsanger.gz | |||
| SRR6260530.fastq.gz | Fastqsanger.gz | |||
| SRR6260540.fastq.gz | Fastqsanger.gz | |||
| SRR6260550.fastq.gz | Fastqsanger.gz |
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Project description:Systemic inflammation drives rapid conversion of conventional CD4+ T cells to Treg in vivo.
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Project description:The immune system faces a task that approximates cognition in its complexity as it processes a multitude of intrinsic and extrinsic signals and integrates these into responses of the appropriate class, specificity, magnitude, and duration for a given threat, with the host’s life often depending on the outcome. CD4+ T lymphocytes occupy a unique role in the generation and regulation of immunity within this context and influence multiple innate and adaptive cell types. With respect to CD8+ cytotoxic T lymphocytes (CTL), CD4+ T cells function early in the response as ‘helpers’ (TH) to increase its magnitude and functionality, and later as regulatory cells (Treg) to restore homeostasis and avoid immune pathology. Using a Listeria monocytogenes (Lm) infection model, we probed whether the conditions of initial pathogen encounter could influence the generation of TH versus Treg. Infection induces rapid polyclonal conversion to functional FoxP3+CD25+ Treg within 24 hours. These findings resolve long-standing questions regarding the requirement for TH and reveal a remarkable degree of plasticity in the function of CD4+ T cells, which can be quickly converted to Treg in vivo in response to acute inflammation.
2021-03-27 | GSE169741 | GEO
Project description:The immune system faces a task that approximates cognition in its complexity as it processes a multitude of intrinsic and extrinsic signals and integrates these into responses of the appropriate class, specificity, magnitude, and duration for a given threat, with the host’s life often depending on the outcome. CD4+ T lymphocytes occupy a unique role in the generation and regulation of immunity within this context and influence multiple innate and adaptive cell types. With respect to CD8+ cytotoxic T lymphocytes (CTL), CD4+ T cells function early in the response as ‘helpers’ (TH) to increase its magnitude and functionality, and later as regulatory cells (Treg) to restore homeostasis and avoid immune pathology. Using a Listeria monocytogenes (Lm) infection model, we probed whether the conditions of initial pathogen encounter could influence the generation of TH versus Treg. At low dose infection, CD4+ T cells ‘help’ CTLs via CD40-CD40L signaling, while high dose infection induces rapid polyclonal conversion to functional FoxP3+CD25+ Treg within 24 hours. These findings resolve long-standing questions regarding the requirement for TH and reveal a remarkable degree of plasticity in the function of CD4+ T cells, which can be quickly converted to Treg in vivo in response to acute inflammation.
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Project description:Analysis of CD4+ cells activated with anti-CD3 and cultured in the presence of IL2. The effects of TGFb and IL6 on Treg conversion were analyzed to discover methods of inhibiting Treg conversion and/or Treg functional inhibition. CD4+ T-cells were enriched from lymph nodes of Foxp3-GFP mice and cultured under the under the following conditions: 1) anti-CD3+IL2; 2) anti-CD3+IL2+TGFβ; 3) anti-CD3+IL2+TGFβ+IL6; and 4) anti-CD3+IL2+IL6. On day 4 cells were collected, stained with anti-CD4-PE, and sorted into CD4+FOXP3- and CD4+FOXP3+ populations (>95% purity). For each treatment condition T-effector cells and Tregs were labeled independently (either cy3 or cy5) and hybridized together for a two-color array experiment. Each treatment condition had dye swapped replicates, and a minimum of 3 replicate in total. Two color experiment. Four conditions : 1) anti-CD3+IL2, 3 samples 2) anti-CD3+IL2+TGFβ, 3 samples 3) anti-CD3+IL2+TGFβ+IL6, 4 samples 4) anti-CD3+IL2+IL6, 3 samples
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Project description:Analysis of CD4+ cells activated with anti-CD3 and cultured in the presence of IL2. The effects of TGFb and IL6 on Treg conversion were analyzed to discover methods of inhibiting Treg conversion and/or Treg functional inhibition. CD4+ T-cells were enriched from lymph nodes of Foxp3-GFP mice and cultured under the under the following conditions: 1) anti-CD3+IL2; 2) anti-CD3+IL2+TGFβ; 3) anti-CD3+IL2+TGFβ+IL6; and 4) anti-CD3+IL2+IL6. On day 4 cells were collected, stained with anti-CD4-PE, and sorted into CD4+FOXP3- and CD4+FOXP3+ populations (>95% purity). For each treatment condition T-effector cells and Tregs were labeled independently (either cy3 or cy5) and hybridized together for a two-color array experiment. Each treatment condition had dye swapped replicates, and a minimum of 3 replicate in total.
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