The Function of Thymic Innate TCRαß+ CD8+ T Cells Is Regulated by Constitutive Expression of B7-H1
Bibliographic record
Abstract
Abstract Abstract 955 Innate T cells display features of Ag-experienced T cells (e.g., high levels of CD44) before any encounter with non-self antigens. They include NKT cells, CD8α/α T cells, as well as an undefined (and presumably very small) proportion of naïve CD4 and CD8 α/β T cells. We used the RAG2-GFP transgenic mouse model to differentiate naïve innate single-positive thymocytes (GFP+CD44high) from re-circulating effector/memory T cells (GFP-CD44high) T cells and naïve conventional (GFP+CD44low) thymocytes. We found that innate T cells represent about 10% of TCRαβ+ single-positive GFP+ thymocytes. To evaluate their proliferative ability under lymphopenic conditions, conventional and innate T cells were sorted and injected in TCRβKO mice. Four weeks later, expansion of conventional T cells was 2.3-fold greater than that of innate T cells. Comprehensive phenotypic analyses of GFP+CD8+CD44low vs GFP+CD8+CD44hi thymocytes revealed that B7-H1 was absent on conventional thymocytes but constitutively expressed on innate CD8+ thymocytes. Moreover, in vitro stimulation of innate T cells with anti-CD3 and anti-CD28 antibodies induced a strong proliferation and secretion of inflammatory mediators such as interferon (IFN)-gamma. The addition of anti-B7-H1 neutralizing antibody, however, inhibited proliferation and IFN-gamma production in a dose-dependent manner. To see whether B7-H1 ligation influenced the viability of CD8+ thymocytes, GFP+CD8+CD44low and GFP+CD8+CD44hi thymocytes were treated for 48 hrs with anti-B7-H1 antibody in vitro then stained for annexin-V and propidium iodine. Under these conditions, 70% of innate GFP+CD8+CD44hi T cells underwent apoptosis as opposed to 30% with conventional thymocytes. To test their bystander properties, we added conventional or innate T cells as third-party cells to an in vitro antigen stimulation assay. Briefly, B6 peritoneal macrophages pulsed with recombinant chicken ovalbumin (rOVA) presented OVA-derived peptides in the context of MHCI, and served as antigen-presenting cells (APCs). For responder cells, we added naive T cells from T cell receptor-transgenic OTI mice that recognize OVA. Interestingly, innate thymocytes were capable of promoting the activation of responding T cells; an effect that was lost upon treatment of innate CD8 T-cells with anti-B7-H1 neutralizing antibody. The sum of these data suggests a role for B7-H1 in the development, survival and proliferation of innate α/β T cells. Acknowledgments Moutih Rafei holds a Fellowship from the CIHR. Claude Perreault holds a Canada Research Chair in Immunobiology. This work was supported by grant # 42384 from the CIHR. Disclosures: No relevant conflicts of interest to declare.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".