Defining early CD8+ T cell responses during acute and chronic viral infection using single-cell RNA-seq analysis
Bibliographic record
Abstract
CD8+ T cells are key in mediating immune responses to viral infections. Viral infections can be acute, in which the infection is resolved, or chronic, when antigen persists. Several studies have illustrated that CD8+ T cells adopt distinct functional states in each infection type. In acute infections, naïve CD8+T cells differentiate into cytotoxic CD8+ T cells and memory CD8+ T cells. In chronic infections, activated CD8+ T cells adopt an altered state known as exhaustion. Exhausted CD8+ T cells lose effector functions and show high expression of inhibitory receptors such as PD-1. Several studies have characterized CD8+ T cell exhaustion at late time-points after a persistent infection has already been established. Recent studies demonstrate that CD8+ T cell exhaustion may be specified during earlier phases of a developing chronic infection. However, these studies do not address the effect of biological sex on early CD8+ T cell responses to chronic infection. Sex differences in susceptibility and outcomes of viral infectious diseases are well-appreciated. Still, the role of sex in the development of CD8+ T cell exhaustion and in the molecular programs underlying CD8+ T cell responses to acute and chronic viral infections remains undefined. This study, therefore, set out to investigate early and sex-based differences in the transcriptional profiles of CD8+ T cells that underlie their responses to acute versus chronic viral infection. The mouse model of acute and chronic lymphocytic choriomeningitis virus infection was used to comparatively analyze transcriptional signatures of single antigen-specific CD8+ T cells during acute versus chronic infection at multiple time-points post-infection. Next sequencing coupled with bioinformatics-based approaches were used to analyze our single-cell RNA sequencing data. Our results reveal an early transcriptional divergence of CD8+ T cells responding to acute versus chronic viral infection. We show that there are sex-specific differences in the transcription profiles, pro-inflammatory cytokine production and clonal expansion of single antigen-specific CD8+ T cells responding to acute versus chronic viral infection at an early time-point and at peak of infection. Overall, the findings in this thesis uncover novel insights into how and when sex differences in CD8+ T cell immunity to acute and chronic viral infection arises and provides the foundation for future sex-based mechanistic studies of CD8+ T cell differentiation.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".