Functional characterization of human T cells generated in vitro from hematopoietic stem cells
Bibliographic record
Abstract
T lymphocytes are a class of white blood cells that play a major role in the adaptive immune response. T cells are generated in the unique microenvironment of the thymus; however, the precise molecular signals enabling their differentiation are still being elucidated. Using the OP9‐DL1 stromal system we have demonstrated the generation of human T cells from umbilical cord‐blood (UCB) hematopoietic stem cells (HSCs). Here, we characterize T cell specification and commitment events induced at both the phenotypic and molecular level examined by the acquisition of T‐lineage cell surface markers and the induction of T cell associated genes, respectively. In addition, in vitro derived T cell subsets are mature and functional as they proliferate and secrete IFNγ following stimulation. Furthermore, we demonstrate the ability of in vitro ‐derived human T cell progenitors to engraft and differentiate into a mouse host thymus in vitro . Finally, HSCs transduced to express an HIV (Human Immunodeficiency virus) inhibitory construct have been generated, and will be evaluated for decreased susceptibility to infection when challenged with HIV. This system has important clinical implications as it provides the foundation for a large supply of human T lymphocyte progenitors, which could be used for the immune‐reconstitution of T cell‐depleted individuals. Research supported by the Ontario HIV Treatment Network (OHTN) and the Canadian Institutes of Health Research (CIHR)
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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) | 0.002 | 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".