I think, many investigators observed T cell markers on the cells of myeloid lineage (neutrophils, monocytes, dendritic cells, eosinophils, macrophages). Evidently, many of these observations can not be fully explained by artifacts due to co-aggregation with T cells. In my laboratory, we really observed TCR beta and gamma chains on 1-3% of neutrophils and CD4 on CD11c+ (dendritic) cells. In available literature, evidence for expression of rearranged chains of TCR and immunoglobulin molecules in myeloid leukemia cells can be found. My interest to these findings was stressed by recently published works by Kerstin Puellmann and Wolfgang Kaminski with co-authors, showing functionality of recombinatorial immune receptors on neutrophils and macrophages (original publication has appeared in PNAS, 2006, 103(39):14441-6.). However, I see continuation of this history still in one laboratory. My personal doubts are evoked by own practice and the reason that we do not see any support for this idea in responses to allogeneic MHC molecules. Although neutrophils can accumulate in the spleen and blood of animals, immunized with MHC class I disparate tumor cells, they cannot do this without CD8 T cells and do not contain elevated percent of TCR bearing cells. So, I am inclined to think, that T cell markers on myeloid cells represent reminders of developmental history of individual cells, deciding to change lineage too late. I would very appreciate further discussion on this issue.
Great discussion topic! It's interesting that neutrophils can express TCR's, my first instinct would be a cell to cell transfer of the receptor, but if there was evidence of expression - that's pretty neat. When I think of unexpected receptors on immune cells I'm reminded of the work of Daniel Davis. (http://www.davislab.ls.manchester.ac.uk/). He's pioneered work on tunneling membrane nanotubes. What's really stuck in my mind is a theory to address why NK cell receptors would be found on recently scanned cells. His group predicted that NK cells would deposit KIR proteins onto the surface of target cells as a way of marking them as "already scanned", thereby improving the speed of subsequent scanning by other NK cells. I'm pretty sure that was just a thought at the end of the discussion and I'm not sure if new papers have come out to prove it, but I thought it was a really interesting way to view receptors that typically are assigned one function. Has your group attempted to see if the neutrophil TCR can engage an MHC successfully or whether any signalling proteins are associated with it?
That's interesting topic! What about an actual gene transfer through phagocytosis? A sort of episomal DNA left over from dead T lymphocytes that continues to be transcribed and produces a functional TCR? Maybe not for neutrophils that have a short half life, but for DCs or tissue-resident macrophages could be the case. What is your idea about that?
Thank you, Felicity! Thank you, Lara! 1) Concerning cell to cell transfer. This would result in some increase in intensity of fluorescence. On the histograms we would see only slight shift of the peaks. Against, neutrophils stained by anti TCR beta are "bright". The intensity of fluorescence is comparable with T lymphocytes. 2) Gene transfer via phagocytosis is very interesting idea, but seems impossible. Too aggressive and inappropriate enzimatic environment in the endocytic pathway leaves few chances for any stable and significant transcription of phagocytosed DNA and expression of proteins. Some microorganisms have capability to survive in phagolysosomes, but this is not the case. Second, I think that DNA in phagocytosed T lymphocytes is degraded.
This is a very interesting topic. Despite nice fluorescence, one cannot exclude passive acquisition of shed receptors. Can you sort the small number of TCR +ve neutrophils and see if they have rearranged TCR Variable genes.
In thymus passive acquisition of T cell differentiation antigens has been described a few decades ago ( I vaguely recall that it is by Dr. Al Singer's group but not positive).
Expression of CD4 on myeloid cells appears to be more frequent in human than in mouse. If I am correct HIV uptake by myeloid cells is indeed via this CD4.
Dear Subbarao, thank you very much for answer! Currently I am so far from final decision and I am trying to estimate possible risks to be involved in this story. I should note that my own experience in this field does not support general idea. I could not see any involvement of TCR expressing neutrophils in allogeneic responses. This should assume either 1) the presence of special forms of TCRs on neutrophils, not reacting with MHC, or 2) nonfunctionality of TCRs molecules on neutrophils, or 3) inconsistency of our analyses.
Sorting of neutrophils is a difficult task - they are very fragile. Theoretically, it is possible to get sequences of rearranged TCRs of neutrophils, but I expect difficulties to put them together with concrete cells, having virtually polyclonal population. To grow individual clones with characterized TCRs would be much more conclusive, but I have not idea, how to force neutrophils to divide.
The problem exists even in definition. In common sense, the cell expressing T cell receptor should be recognized as T cell.
So, I very appreciate real experience of other scientists irrespective of that, positive or negative.
This may not be relevant to this very interesting discussion, however I wanted to ask a question here. I am a cancer biologist (with not much immunology background) who just began looking at the immune infiltration in mouse tumors using CyTOF technology. I have repeatedly seen expression of TCRgd on myeloid (CD11b+) cells in SPADE analysis of CyTOF data. Is anyone familiar with this phenomenon?
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