IL-7 is essential for accumulation of antigen-specific CD8 T cells and to generate clonotype-specific effector responses during airway influenza/A infection
Bibliographic record
Abstract
Abstract Airborne diseases are the leading cause of infectious disease-related deaths in the world. In particular, the influenza virus activates a network of immune cells that leads to clearance or an overzealous response that can be fatal. Tight regulation of the cytokines that enable proper activation and function of immune cells is necessary to clear infections efficiently while minimizing damage to the host. Interleukin-7 (IL-7) is a cytokine known for its importance in T cell development and survival. How IL-7 shapes CD8 T cell responses during an acute viral infection is less understood. We had previously shown that IL-7 signaling deficient mice have reduced accumulation of influenza-specific CD8 T cells following infection. We sought to determine whether IL-7 affects early CD8 T cell expansion in the mediastinal lymph node and effector function in the lungs. Using IL-7Rα signaling deficient mice, we show that IL-7 is required for a normal sized mediastinal lymph node and the early clonal expansion of antigen-specific CD8 T cells therein. Bone marrow chimeric models and adoptive transfer of transgenic TCR CD8 T cells reveal a cell-intrinsic role for IL-7 in the accumulation of NP 366–374 and PA 224–233 -specific CD8 T cells. We also found that IL-7 dictates terminal differentiation, degranulation and cytokine production in PA 224–233 -specific but not NP 366–374 -specific CD8 T cells. We further demonstrate that IL-7 is induced in the lung tissue by viral infection and we characterize multiple cellular sources that contribute to IL-7 production. Drugs that manipulate IL-7 signaling are currently under clinical trial for multiple conditions. Our findings on IL-7 and its effects on lower respiratory diseases will be important for expanding the utility of these therapeutics. Author Summary Interleukin-7 plays an important role in development of immune cells such as lymphocytes. In recent years, its role in the immune system has been expanded beyond the development of immune cells to include revitalizing of lymphocytes during tumor and chronic viral response. We show here that IL-7 is required for accumulation and function of specialized lymphocytes in the lungs during an acute influenza infection.
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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 | 0.001 |
| 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".