MALT1-deficient CD4 T cells exhibit decreased IL-2 secretion and impaired Th1 and Th17 differentiation
Bibliographic record
Abstract
Abstract A child admitted to British Columbia Children’s Hospital displayed a novel clinical presentation of immune dysregulation, exhibiting lymphocytic infiltration and severe inflammation of the intestinal tract and other mucosal surfaces. Whole-exome sequencing revealed that the patient inherited missense MALT1 mutations and her lymphocytes exhibited deficits in MALT1 protein and MALT1-dependent signal transduction. MALT1 plays critical roles in T cell receptor signal transduction through at least two different mechanisms: (1) as a signaling adaptor molecule bringing together CARMA-1 and BCL-10 to form the CBM signalosome complex and (2) as a caspase-like protease (paracaspase) cleaving substrates after arginine residues. Studies on Malt1−/− mice have revealed diminished NF-KB activation and weakened T cell immunity whereas mice lacking paracaspase activity but not MALT1 adaptor function are prone to lethal autoimmunity. Altogether, these mouse findings raise questions regarding the nature of our patient’s mutant MALT1 protein and the role it plays in her proinflammatory phenotype. Consequently, we plan to analyze our patient’s MALT1 mutation by investigating the paracaspase activity, signaling, and function of her T cells. Early studies have found that patient CD4 T cells exhibit defects in Th1 and Th17 differentiation and these impairments could be responsible for inefficient immune responses leading to chronic infections. Finally, a better understanding of MALT1 will provide insight into inflammatory disease and prove invaluable in supporting MALT1-targeted therapies to modulate T cells to treat autoimmune diseases.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".