The expression and signal transduction of CD4, an HIV and interleukin-16 receptor, in monocytic cells.
Bibliographic record
Abstract
The down-regulation of CD4 by cultured monocytes has been observed by our group and by other investigators. Flow cytometric analysis was performed to elucidate factors influencing this phenomenon. The addition of LPS, GM-CSF, M-CSF or IL-10 to monocyte cultures failed to inhibit the decrease in monocyte CD4 expression following overnight culture. The down-regulation was an adherence-independent phenomenon since it was not prevented by culture in Teflon vials. The type of anticoagulant into which the peripheral blood was collected did not appear to be a factor, The presence or absence of lymphocytes within the cultures was also inconsequential. The continued culture of monocytes in a whole blood environment resulted in decreased CD4 down-regulation. Experiments in which CD4 was tagged with alpha-CD4-PE mAb prior to cell culture revealed that the down-regulation observed was the result of CD4 internalization. In an attempt to further understand monocyte CD4 function, we investigated the role of monocyte CD4 in signal transduction. Stimulation of Thp-1 monocytic cells with antibody to CD4 resulted in a Ca2+ flux, as well as in the time-dependent tyrosine phosphorylation of various proteins having molecular weights of approximately 180, 140, 120, 110, 85, 65, 55, 50 and 35 kDa. We identified the 140 and 85 kDa proteins as PLC-gamma1, and the regulatory subunit of PI3-K, respectively. Using immunoprecipitation/Western immunoblotting, we were unable, however, to show any direct association between CD4 and PLC-gamma1, PI3-K, or other signaling proteins. In an attempt to identify proteins capable of associating with the cytoplasmic tail of CD4, we generated a GST-CD4cyt fusion protein for use in far Western blots and immunoprecipitation experiments. In both types of experiments, the GST-CD4cyt fusion protein routinely associated with 45 and 55 kDa proteins. In the immunoprecipitation experiments, a 35 kDa protein was also observed. The above results suggest that the expression of monocytic CD4 is regulated during the differentiation process. Furthermore, the cytoplasmic tail of monocytic CD4 is associated with various proteins which we postulate function in signal transduction, and which may also play a role in CD4 down-regulation.
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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) | 0.001 | 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".