Requirement for CD2 signaling in the costimulation and induction of murine cytotoxic T lymphocytes
Bibliographic record
Abstract
Although signal transduction through CD2 is known to be involved in T cell activation, the costimulatory role of CD2 in cytotoxic T lymphocyte development is not entirely clear. CD2 is a surface molecule found on most thymocytes and all mature T cells which is known to function in adhesion and the regulation of cytokine production and responsiveness. In this study, we show that the interaction of CD2 with its ligand CD48 is critical for the induction of cytotoxic effector function by T lymphocytes since anti-CD3-activated killer T (AK-T) cell induction is inhibited in the presence of anti-CD2 and anti-CD48 monoclonal antibodies (mAb). Inhibition is due to decreased conjugation of effector cells to allogeneic target cells and decreased cytolytic molecule expression. One likely explanation for the observed inhibitory effects is that CD2 blockade downregulates IL-2 and IFN-gamma synthesis. Both IL-2 and IFN-gamma are of critical importance for the development of T cell cytotoxicity. Evidence is provided that blockade of CD2--CD48 interactions resulted in decreased IL-2 and IFN-gamma protein and mRNA expression in anti-CD3 activated T cell cultures. Furthermore, culture in the presence of anti-CD2 mAb downregulated perforin and granzyme B mRNA transcripts in AK-T cells. Granzyme B and perforin are two key molecules in the granule-mediated pathway of killing. Moreover, downregulation of baseline perforin expression in anti-CD2 mAb treated AK-T cell cultures, as well as decreased background perforin expression in resting T cells exposed to anti-CD2 mAb indicates that CD2 may have negative signaling properties. Restoration of granzyme B and perforin expression, as well as AK-T cell effector function upon addition of exogenous IL-2 and IFN-gamma to anti-CD2 mAb treated AK-T cells at initiation of culture is consistent with the cytokine-dependent nature of the granzyme B/perforin cytolytic machinery. Although signaling through CD28 and LFA-1 has been implicated in enhancing the stability of mRNAs coding for IL-2 and IFN-gamma, little is known about the role of CD2 signaling in cytokine mRNA stabilization. Here, we show that CD2 signaling enhances the stability of both IFN-gamma and IL-2 mRNA. These results confirm the costimulatory role of CD2 in T cell induction and suggest that inhibition of T cell activation and consequent effector responses by CD2--CD48 blockade involves changes in IL-2 and IFN-gamma mRNA stability. In conclusion, the results of this study indicate that costimulatory signaling through CD2 is critical for the development of cytotoxic T cell activity.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".