P16-30. Induction of Tim-3 expression by the common gamma-chain cytokines IL-2, IL-7, IL-15 and IL-21
Bibliographic record
Abstract
Tim-3 expression is upregulated in HIV-1-infected individuals, and has been implicated in driving T cell exhaustion. While expression is disproportionately high on HIV-1-specific CD8+ T cells, >70% of total CD8+ T cells in the peripheral blood of infected individuals have been observed to express Tim-3, suggesting the existence of a more general mechanism of induction. Thus, Tim-3 may contribute not only to an impairement of virus-specific responses, but also tp a more generalized immunosuppression. The mechanisms leading to this global upregulation of Tim-3 expression remain unknown. Isolated CD4+ T cells were infected with HIV-1 in vitro. Whole PBMC, and isolated CD4+ or CD8+ T cells were treated with stimuli including LPS, and cytokines. Tim-3 expression was analyzed at various time-points by flow cytometry, in conjunction with a number of phenotypic markers and CFSE. Upon removal of cytokine, apoptosis (annexin-V) was analyzed along with Tim-3 expression. In vitro HIV-1-infection had no effect on the Tim-3 expression levels of CD4+ T cells. The common gamma-chain cytokines induced high levels of Tim-3 expression with IL-15>IL-2>IL-21>IL-7, while LPS and IL-4 had no effect. The gamma-chain cytokines induced distinct profiles of Tim-3/PD-1 co-expression with some driving a dual-positive population, and other preferentially upregulating either Tim-3 or PD-1. Tim-3 expression was primarily limited to cells that had undergone proliferation in response to cytokine, and these cells preferentially underwent apoptosis upon cytokine removal. We provide evidence against the direct exposure of T cells to virus, or exposure to LPS as etiologies for global Tim-3 upregulation in HIV-1 infected individuals. Potent upregulation of Tim-3 is however driven by exposure of T cells to common-gamma chain cytokines. Physiologically, this upregulation likely serves to balance the survival signals provided by these cytokines, and to drive the elimination of these activated cells upon removal of cytokine (resolution of infection).
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".