Defective interleukin-2-dependent STAT5 signalling in CD8 T lymphocytes from HIV-positive patients
Bibliographic record
Abstract
BACKGROUND: CD8 T lymphocytes are critical in the control of HIV replication and disease progression. Our previous studies demonstrated that CD8 T cells from chronically infected patients with high virus load proliferated poorly in response to interleukin-2 (IL-2), a cytokine critical in CD8 T cell growth and differentiation, even though relatively high levels of IL-2 receptor (IL-2R) were expressed. This suggested that signal transduction defects in response to IL-2 might be involved. The STAT5 transcription factor is important in IL-2-dependent biological responses and it is known that there are defects in unstimulated CD3 and CD4 cells in HIV-infected patients. OBJECTIVE: To investigate whether the induction of STAT5 by IL-2 is altered in the CD8 T cells from HIV-positive individuals and the impact of highly active antiretroviral therapy (HAART) on its status. METHODS: CD8 T lymphocytes were purified from the peripheral blood mononuclear cells of HIV-positive patients before and after HAART. Ex vivo IL-2-induced STAT5 activation was evaluated by immunoblotting and electrophoretic mobility shift assays. RESULTS: CD8 T cells from a subset of untreated HIV-positive patients were unable to activate STAT5a and STAT5b proteins functionally in response to IL-2. This defect was not a result of alterations in IL-2R expression but correlated with an impaired activation of the upstream kinase Jak-3, known to mediate STAT5 activation. Overall, HAART restored Jak/STAT signalling in such patients. CONCLUSIONS: These results further uncover a potential mechanism by which CD8 T cell function is impaired in HIV-infected patients.
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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 | 0.000 |
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".