A liver-infiltrating CD4+ Tfh1 cell response predicts HCV control, hepatitis, and seroconversion during acute infection
Bibliographic record
Abstract
Sustained CD4+ T cell immunity is required for resolution of acute hepatitis C virus (HCV) infection, but the response remains poorly characterized. Here, circulating CD4+ T cells with high programmed cell death 1 (PD-1) and ICOS coexpression were temporally associated with onset of virus control, seroconversion, and hepatitis in HCV-infected chimpanzees. Coproduction of T follicular helper (Tfh) (IL-21 and CXCL13) and Th1 (IFN-γ and TNF) cytokines after stimulation with HCV nonstructural proteins demonstrated that the response was predominately Tfh1 like and virus specific. Transcriptional analysis verified a Tfh1 lineage assignment. Effector-related genes such as ADGRG1 (GPR56), ZNF683 (Hobit), and KLRB1 (CD161) were also expressed. HCV-specific PD-1hiICOShi CD4+ Tfh1-like cells were enriched in liver, suggesting the potential for B and CD8+ T cell help at the site of virus replication. Most circulating and intrahepatic PD-1hiICOShi CD4+ Tfh1-like cells did not express CXCR5 and therefore resembled CXCR5-CXCL13+ peripheral helper cells that infiltrate tumors and tissues inflamed by autoimmunity. PD-1hiICOShi CD4+ Tfh1-like cells also peaked after hepatitis A virus infection, but the response was accelerated by several weeks compared with HCV infection. The PD-1hiICOShi phenotype and temporal association between the peak response and alanine aminotransferase may provide markers to guide human studies of CD4+ T cell immunity against HCV and other hepatotropic viruses.
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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 | 0.000 |
| 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".