Overcoming CD4 T helper cell fate restrictions to enhance CD8 T cell and B cell immunity to control persistent LCMV infection
Bibliographic record
Abstract
Abstract Persistent viral infection inhibits CD4 Th1 responses, resulting in loss of the CD8 T cell helping Th1 subset and accumulation of B cell helping Tfh cells. Yet, the mechanisms that inhibit CD4 Th1 differentiation and the repercussions of loss of Th1 cells on viral control are unclear. Herein, we demonstrate that the dual upregulation of PD-L1 and IL-10 by chronic type I interferon (IFN-I) signaling during persistent infection suppresses CD4 Th1 priming. Therapeutic blockade of IL-10R and PD-L1 could restore the differentiation of new CD4 Th1 cells, highlighting a new function for PD-L1 to co-inhibit CD4 Th1 priming and identifying a new combinatorial suppressive mechanism during persistent infection. However, CD4 Th1 cells generated by blocking IFN-I signaling in vivo could not be sustained, giving way to a Tfh based response and predominant help to B cells. In vitro polarized virus-specific CD4 Th1 cells also converted towards Tfh cells, however maintained a population of Th1 cells that could enhance exhausted CD8 T cell responses and promote augmented viral clearance. Interestingly, virus-specific CD4 Th17 and Treg cells were also redirected towards Tfh as persistent infection progressed. Thus, our studies have important implications for stability of de novo activated and immunotherapeutic T cells and demonstrate that the redirection away from Th1 responses is a mechanism of immunosuppression to limit the control of persistent viral infection.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 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".