IL-7 and the HIV Tat protein act synergistically to down-regulate CD127 expression on CD8 T cells
Bibliographic record
Abstract
IL-7 signaling is essential for optimal CD8 T cell function, homeostasis and establishment of memory. We have previously shown decreased expression of the IL-7 receptor alpha-chain (CD127) on CD8 T cells from HIV-infected patients with active viral replication. We have also shown that soluble HIV Tat protein specifically down-regulates CD127 on the surface of CD8 T cells and impairs cell proliferation and cytolytic potential following stimulation with IL-7 in vitro. We now show that soluble HIV Tat protein and IL-7 at near physiologic concentrations act synergistically to suppress CD127 expression. While soluble HIV Tat protein and IL-7 both independently reduce CD127 expression on the surface of CD8 T cells, Tat concentrations of 10 microg ml(-1) and IL-7 concentrations of 500 pg ml(-1) are required in vitro to have an appreciable effect. However, where 0.5 microg ml(-1) of Tat has no effect on CD127 expression and 200 pg ml(-1) of IL-7 decreases CD127 by only 14%, these two together at these same concentrations induce a 35% reduction in CD127 expression after 24 h. Inhibition of Janus kinase (JAK) completely blocks IL-7's ability to down-regulate CD127 on the surface of CD8 T cells and also abolishes synergy with Tat. Interestingly, while Tat acts synergistically with IL-7 to reduce CD127 expression, it antagonizes IL-7-induced cell proliferation and Ki-67 expression and has no effect on IL-7-mediated signal transducer and activator of transcription 5 (STAT5) phosphorylation or expression of the anti-apoptotic gene Bcl-2. Thus, by affecting different IL-7 signal transduction pathways, HIV Tat protein is able to impair both CD8 T cell activation and proliferation without inducing apoptosis.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.001 | 0.004 |
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 teacher head, 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".