Immune ontogeny and lymphocyte responses to primary herpesvirus infections in Ugandan infants
Bibliographic record
Abstract
Herpesviruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV) cause an enormous burden of disease worldwide. Congenital CMV (cCMV) is the most common congenital infection in the world and can cause deafness and intellectual disability. EBV is the causal agent of Burkitt’s lymphoma (most common pediatric cancer in Africa), infectious mononucleosis, and associated with several autoimmune diseases. Age-related differences in symptoms and diseases caused by all herpesviruses likely reflect immune variation early in life, however lymphocyte responses to EBV and CMV are not well documented in young children. Gamma delta (γδ) T cells develop early in gestation and may be important for controlling CMV infection before alpha beta T cell immunity develops. Indeed, a “public” (shared among many individuals) γδ T cell receptor (TCR) clone has been associated with cCMV and may represent an important early response to the virus. In this study we aimed to describe general immune ontogeny and lymphocyte responses to herpesvirus infections in infancy and comprehensively characterize γδ T cell responses to CMV infection in infants. Following a birth cohort of 32 Ugandan infants and their mothers during their first year of life, we captured 20 CMV and 10 EBV primary infections. Using standard flow cytometry, we characterized a wide range of innate and adaptive lymphocytes and further characterized the γδ T cells from a subset of the cohort with a 21-color spectral flow cytometry panel and extracted RNA for TCR sequencing. In the first year of life, there were significant ontological changes within all lymphocyte subsets tested (natural killer (NK) cells, B cells, T cells). NK and T cell compartments experienced the most dramatic changes with CMV infection. Age and CMV infection were correlated with γδ T cells and EBV was not. Unsupervised clustering analyses revealed CMV-specific adaptive-like γδ T cell subsets with effector phenotypes in infants and adults. Our findings provide evidence of the cell types involved in primary herpesvirus infections during infancy and support the notion that γδ T cells are participating in the immune response to CMV infection in early life, providing insight for novel new vaccine designs to more effectively prevent CMV-related disease.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| 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".