294 B CELL MODULATION BY TOXIC SHOCK SYNDROME TOXIN-1 INDUCED CD25+ VERSUS CD25- CD4+ REGULATORY T CELLS GENERATED IN BALB/C MICE
Bibliographic record
Abstract
Purpose T regulatory (Treg) cells, comprising only 5-10% of the peripheral CD4+ T cell population, are known to suppress T cell function in the host immune response. One subtype of Tregs is the Treg-1 (Tr1) cells, which can be generated in Balb/c mice following repeated subcutaneous injection of Toxic Shock Syndrome Toxin-1 (TSST-1), a superantigen secreted by Staphylococcus aureus. The purpose of this study is to assess the modulating effects of TSST-1 induced Tregs on the proliferation and apoptosis of murine B cells in response to TSST-1. Methods 6-8 week-old female BALB/c mice (n = 6) were administered 4 μg TSST-1 or PBS subcutaneously for 3 doses at 4-day intervals. Mice were sacrificed 2 h after the last injection, and splenocytes were obtained. CD4+CD25+ and CD4+CD25- T cells were purified by magnetic separation. Both groups of CD4+ T cells were co-cultured in a 1:1 ratio with splenic B cells from naïve mice, and restimulated with 1 nM TSST-1 for 3 days in vitro. Co-cultures were treated with anti-CD19-allophycocyanin (APC) to identify the B cell population. Carboxyfluorescein diacetate succinimidyl ester (CFSE) staining was used to track B cell proliferation, and 7-amino actinomycin D (7-AAD) was employed to assess apoptosis. Results Co-culturing with PBS primed CD4+CD25- T cells in the presence of 1nM TSST-1 caused B cells to undergo at least 3 cycles of proliferation. In contrast, co-culturing with either TSST-1 primed CD4+CD25+ or CD4+CD25- T cells inhibited progression of B cell proliferation (p≤0.05; student t test). 7-AAD staining revealed that TSST-1 primed CD4+CD25+ Tregs in the presence of TSST-1 prevented B cell proliferation by inducing B cell apoptosis. On the other hand, TSST-1 primed CD4+CD25- Tregs did not cause B cell apoptosis, but prevented B cell proliferation likely by down-regulating CD19 expression. Conclusion These data provides evidence that in addition to modulating T cell activity, TSST-1 induced Tregs also regulate B cell proliferation and apoptosis in response to TSST-1 re-stimulation in vitro. Furthermore, CD4+CD25+ and CD4+CD25- Tregs appear to have different mechanisms of action. These results raises the possibility of using TSST-1 primed CD4+CD25+ or CD4+CD25- Tregs for controlling B cell-mediated autoimmune diseases, such as rheumatoid arthritis or systemic lupus erythematosis.
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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) | 0.001 | 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 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".