Regulation of T cell CD5 levels by BTLA
Bibliographic record
Abstract
Abstract Many coinhibitory receptors are absent from naïve T cells and upregulated upon activation. In contrast, there are a small number of coinhibitory receptors expressed constitutively by naïve T cells, including CD5, BTLA, and VISTA. The relationship between these constitutively expressed coinhibitors is unknown. We examined the relationship between the constitutively expressed BTLA and CD5 in T cell ontogeny. We found an inverse relationship between CD5 and BTLA expression levels, with low BTLA expression in the thymus and higher BTLA expression in the periphery, corresponding with high and low CD5 expression, respectively. To determine if there is a causal relationship between BTLA expression and CD5 expression, we examined CD5 expression in wild type (WT) vs. btla−/− T cells. Interestingly, btla−/− T cells consistently expressed higher levels of CD5 both in thymic and splenic CD4 and CD8 T cells, indicating that BTLA expression directly or indirectly determines the level of CD5 expression broadly across T cells. In contrast, the loss of an inducible coinhibitor, PD-1, only affected CD5 levels on splenic CD8+ T cells. The loss of BTLA expression early in ontogeny might alter the TCR repertoire indirectly affecting CD5 levels, or instead its loss might affect CD5 expression rapidly within mature T cells. To examine the latter, we deleted btla by administering tamoxifen to adult btlafl/fl CreERT2+/− mice and WT CreERT2+/− controls. Loss of btla in adults led only to a transiently heightened CD5 expression. Together our data indicates that loss of BTLA early, but not later in ontogeny, leads to a long-term increase in CD5 expression by T cells. Such calibration of CD5 levels early in ontogeny might serve to reduce autoimmunity. Funded by the CIHR, NSERC, and an AAI fellowship; btlafl/fl mice provided by the La Jolla Institute for Immunology.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".