Reduced CCR4, interleukin‐13 and GATA‐3 up‐regulation in response to type 2 cytokines of cord blood T lymphocytes in infants at genetic risk of type 1 diabetes
Bibliographic record
Abstract
Aberrancies in T-cell polarization including expression of chemokine receptors have been reported in human leucocyte antigen (HLA) class II associated autoimmune diseases, such as type 1 diabetes (T1D) and rheumatoid arthritis. We asked whether these aberrancies are present at birth in newborn infants carrying the HLA risk haplotypes for T1D. Sixty-seven cord blood (CB) samples from infants were screened for T1D-associated HLA risk genotypes (HLA-DR4-DQ8 and/or DR3-DQ2 without protective alleles). CB lymphocytes were stimulated with phytohaemagglutinin in type 1 (interleukin (IL)-12, anti-IL4) or type 2 (IL-4, anti-IL12) cytokine environment for 6 days. The expression of chemokine and cytokine receptors on T cells was determined by flow cytometry, secretion of cytokines was analysed with enzyme-linked immunosorbent assay, and transcription factors were analysed using real-time reverse transcriptase-polymerase chain reaction. After culture of CB lymphocytes in type 2 cytokine environment newborn infants carrying DR4-DQ8 haplotype (n=18) showed reduced percentage of CD4 T cells expressing CCR4 (P=0 x 009) and the level of CCR4 mRNA was decreased (P=0 x 008). In addition, lower secretion of IL-13 and expression of GATA-3 in CB lymphocytes cultured in type 2 cytokine environment were found in the infants with DR4-DQ8 haplotype (P=0 x 020 and P=0 x 004, respectively) in comparison to newborn infants without DR4-DQ8 and DR3-DQ2 haplotypes (n=37). Poor in vitro induction of type 2 immune responses in newborn infants with DR4-DQ8 haplotype suggests that the HLA genotype associated with risk of autoimmunity may affect the T cell polarization already at birth, which in turn may contribute to the risk for autoimmunity later in life.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".