Suppression of Immunodominant Antitumor and Antiviral CD8+ T Cell Responses by Indoleamine 2,3-Dioxygenase
Bibliographic record
Abstract
Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-degrading enzyme known to suppress antitumor CD8(+) T cells (TCD8). The role of IDO in regulation of antiviral TCD8 responses is far less clear. In addition, whether IDO controls both immunodominant and subdominant TCD8 is not fully understood. This is an important question because the dominance status of tumor- and virus-specific TCD8 may determine their significance in protective immunity and in vaccine design. We evaluated the magnitude and breadth of cross-primed TCD8 responses to simian virus 40 (SV40) large T antigen as well as primary and recall TCD8 responses to influenza A virus (IAV) in the absence or presence of IDO. IDO(-/-) mice and wild-type mice treated with 1-methyl-D-tryptophan, a pharmacological inhibitor of IDO, exhibited augmented responses to immunodominant epitopes encoded by T antigen and IAV. IDO-mediated suppression of these responses was independent of CD4(+)CD25(+)FoxP3(+) regulatory T cells, which remained numerically and functionally intact in IDO(-/-) mice. Treatment with L-kynurenine failed to inhibit TCD8 responses, indicating that tryptophan metabolites are not responsible for the suppressive effect of IDO in our models. Immunodominant T antigen-specific TCD8 from IDO(-/-) mice showed increased Ki-67 expression, suggesting that they may have acquired a more vigorous proliferative capacity in vivo. In conclusion, IDO suppresses immunodominant TCD8 responses to tumor and viral antigens. Our work also demonstrates that systemic primary and recall TCD8 responses to IAV are controlled by IDO. Inhibition of IDO thus represents an attractive adjuvant strategy in boosting anticancer and antiviral TCD8 targeting highly immunogenic antigens.
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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) | 0.001 | 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) | 0.001 | 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".