The character of anti-HCV T cell responses differs between spontaneous and treatment-induced viral clearance s
Bibliographic record
Abstract
Introduction: Hepatitis C virus (HCV) is a common infection with approximately 170 million individuals infected worldwide. The majority of exposed individuals develop chronic infection, with viral clearance being the exception to the rule. Even with antiviral therapy, only 50-75% of treated individuals become HCV RNA negative. The role of the adaptive immune response, and particularly T cells, has been well established in other viral infections but its function in HCV infection is unclear, making it difficult to develop either prophylactic or therapeutic vaccine strategies. Objectives: Compare the breadth, specificity, and magnitude of anti-HCV T cell responses in individuals who are chronically HCV-infected with those who clear HCV spontaneously or after antiviral treatment. Methods: We assessed T cell responses in 3 groups of HCV exposed individuals: 18 people who were chronically HCV infected (anti-HCV antibody and HCV RNA positive), 5 who were exposed to HCV but cleared the virus without treatment (antibody positive, RNA negative), and 17 who responded to anti-HCV treatment (antibody positive but RNA negative after treatment). CD4+ T cell responses to HCV and recall antigens were measured by standard 3H-thymidine proliferation assay, and CD8+ T cell responses were evaluated by incubating peripheral blood mononuclear cells (PBMC) overnight with 15-mer peptides spanning the entire HCV-1a genome. The number of HCV-specific interferon-gamma (IFN-g)-producing cells per million PBMC was estimated by ELISPOT. Results: Anti-HCV CD4+ T cell responses were uncommon, and of low magnitude in all groups. Responses were only to peptides in the core region. The overall breadth of the anti-HCV CD8+ response was greatest in treated responders (average 43/44 peptide pools tested positive) and least in those who failed treatment (average 11/44). All clearers had responses to the NS5 region. The magnitude of the CD8+ response tended to be highest in the treated responders, but there was no significant difference between groups. Conclusions: The character of the anti-HCV T cell response differs not just between chronic infection and clearance, but also between spontaneous versus treatment-associated HCV clearance. This suggests that it is likely a combination of T cell breadth, magnitude and specificity that results in viral clearance. Based on these results, development of therapeutic and prophylactic vaccine strategies may need to target different T cell responses.
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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 | 0.001 |
| 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) | 0.003 | 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".