ArticleScience advances2022
BCG vaccinations drive epigenetic changes to the human T cell receptor: Restored expression in type 1 diabetes.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Review
- Long-Term Impact of Historical BCG Vaccination Policies on Parkinson's Disease Risk: A Hypothesis-Generating Retrospective Cohort Analysis.Biomedicines · 2026Article
- BCG Impact on PD-1/PD-L1 Expression in Peripheral Immunocytes of Cancer Patients-A Potential Explanation for Its Activity in Preventing Alzheimer's Disease.Current issues in molecular biology · 2025Article
- Long-term DNA methylation changes mediate heterologous cytokine responses after BCG vaccination.Genome biology · 2025Article
- The Current Status of T Cell Receptor (TCR) Repertoire Analysis in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Late in the US pandemic, multi-dose BCG vaccines protect against COVID-19 and infectious diseases.iScience · 2024Article
- Article
- DNA Vaccines: Their Formulations, Engineering and Delivery.Vaccines · 2024Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The BCG (Bacille Calmette-Guérin) vaccine, introduced 100 years ago for tuberculosis prevention, has emerging therapeutic off-target benefits for autoimmunity. In randomized controlled trials, BCG vaccinations were shown to gradually improve two autoimmune conditions, type 1 diabetes (T1D) and multiple sclerosis. Here, we investigate the mechanisms behind the autoimmune benefits and test the hypothesis that this microbe synergy could be due to an impact on the host T cell receptor (TCR) and TCR signal strength. We show a quantitative TCR defect in T1D subjects consisting of a marked reduction in receptor density on T cells due to hypermethylation of TCR-related genes. BCG corrects this defect gradually over 3 years by demethylating hypermethylated sites on members of the TCR gene family. The TCR sequence is not modified through recombination, ruling out a qualitative defect. These findings support an underlying density defect in the TCR affecting TCR signal strength in T1D.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.