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All issues indicated by the reviewers were addressed and revised manuscript is acceptable now.
[# PeerJ Staff Note - this decision was reviewed and approved by Gwyn Gould, a PeerJ Section Editor covering this Section #]
The language has improved, however there are still minor word choice errors that need to be addressed.
The authors have made improvements to the manuscript based on my previous suggestions.
My previous suggestions have been addressed by the authors and has improved the manuscript and figures.
Please address concerns of both reviewers and amend manuscript accordingly.
The term “germs” is not professional (comment noted) also “necessitates” (line 126) appears to be off. The way it is written it seems to say “In humans, the development of γδT cells makes it so TCR signaling requires sustained Notch signaling…”
The English is clear, unambiguous, and technically correct text.
Figure 2 “perferin” appears off as well as Figure 1 “peripherul”
In figure 2 I am not sure why fungal is listed as pro or anti. I am sure that is the case but there is no information in the article. If that is due to word limitations that is probably fine. I see the sentence in Fig 2 description. The goal of this article is to convey the evidence and allow the reader to decide for themselves. Why do you say V delta 1 cells are pro-infective? If you don’t want to get into the evidence you can say something like, “several studies state…”
Literature references seem to be limited to post 2018. I cited 3-4 articles you may find useful.
The methodology should be a more robust. I do not think the literature review needs to find every article ever written but the authors should state what search terms were used, how many articles were found, and how many duplicates there were etc… It appears they limited their search criteria to humans. Was there a reason 2019 was picked as a cutoff year? They should state any other exclusion criteria. A PRISMA figure for depicting this would be helpful. The there are too many search terms perhaps summarize them and place them in supplemental information.
I found the headings on each section helpful and the paper is well organized.
Yes, the topic is of interest and I feel it represents the cutting edge of the field.
Vδ1+ T cells have been reviewed recently in cancer immunotherapy but not infectious disease. The topic is interesting, important and novel.
Methods should be more detailed as discussed above.
Some of the inferences drawn from the material did not seem congruent.
For example, I did not think this statement was appropriate “Collectively, these findings underscore the critical role of Vδ1+ T cells in orchestrating the immunological response against human malaria.” Based on the data shared the Vδ1+ T cells may well be harmful (just like neutrophils in COVID, eosinophils in allergy). Perhaps there was more data that was not shared.
There are adequate citations, however I felt many statements were too general.
The review is organized logically into coherent paragraphs and subsections.
This is important and new. This is a niche area.
As discussed above, the author implies in several areas that because the V delta 1+ cells respond in an infection it does not mean it is helpful. Two examples are given.
I would be interested to know how the author would apply this knowledge. Do the authors believe immunostimulants targeting Vδ1+ T cells would be helpful? Should we be apply chimeric T cell techniques to the Vδ1+ T cells in order to optimize effectiveness?
The conclusion does identify appropriate questions. Some of it is too vague but it is all well supported. The authors should also feel accomplished in making this article concise. In that sense it is well-written.
I would ask why the IUIS has not identified any Vδ1+ T or even γδT related immunodeficiencies. Perhaps their absence is not compatible with life? Alternatively, perhaps when absent no immunodeficiency exists? This is an area where it may be appropriate to reference murine studies. Wonderful article. Please keep adding to this
n/a
The topic of this review is of broad interest given the range of immune responses Vδ1 γδ T cells can have a role in. This field is however extensively reviewed elsewhere and at this stage this review does not offer any new insights or perspectives on the field but rather serves as a brief overview.
Major point:
1. The first paragraph of the introduction (line 32-39) is too generalised and in lay language rather than scientific. This should be re-written in more scientific language and be more specific to the topic of this review.
The review is organised in a mostly logical way but it does suffer from a lack of specificity and depth in areas.
Major points
1. There has been a great deal of human based research for CMV infection and Vd1 γδ T cells particularly post-transplant - so I am unsure why this was not given a section in this review? As in the discussion line 231 you suggest the majority of research findings have been in mice which is not accurate.
2. Referencing is not comprehensive enough in places, often only a single reference or review article reference is given rather than citing the original research papers that made the first findings.
3. The discussion is vague in places, with lines like 233-234 “further investigation into Vd1+ T cells is warranted to garner increased attention” does not add any informative insights. Consider writing with more critical appraisal and your perspective of the literature rather then making generalised statements.
There are some issues with the validity of the descriptions and interpretations within the review.
Major points:
1. There are often vague statements made e.g. line 130 “The expression of these chemokine receptors undergoes significant changes in response to different physiological conditions”. What changes do you mean? And what physiological conditions? Similarly line 118 “γδ T cells originate from T-cell precursors originating from bone marrow hematopoietic stem cells” but you do not discuss that the notch-dependent DP and notch independent DN developmental pathways. This lack of specific information weakens the review.
2. Line 125 “the precise age at which Vd1+ T cells proliferate remains unknown” is not correct. Your ref 9 has done comprehensive analysis of the frequency of γδ T cell subsets during aging from infant to adult and this needs to be addressed and discussed here.
3. Line 90-92 states: “So, besides TCR-based sorting, we can also group γδT cells into innate and adaptive immune cells based on their gene expression profiles or immune responses” but then you go on to categorise innate as Vd2 and adaptive as Vd1 which is doing so based on the TCR and not based on their gene expression profiles or immune responses as you previously state. This needs to be re-written to be clearer.
4. Line 141: “undergo rapid clonal expansion in response to antigenic stimuli from tumors or infectious agents, unlike Vg9Vd2+ T cells. This is misleading, as Vd2 cells do undergo rapid clonal expansion in response to their antigen (HMBPP) and in response to certain infections - and is not supported by the reference you provide [23].
5. Line 234-235: Vd1+ T cells have been observed to be “differentially expressed” is incorrect, the cells are not “expressed” they are either present or their transcriptional profiles are “differentially expressed”.
1. Figure 1 is incorrect and needs major revising. Showing the Vd1 arrow coming from the thymus makes it seem like this is the only place these cells are located, rather then highlighting their mucosal/organ distribution. Then separating the population to adaptive-like and innate-like is incorrect as all Vd1 are considered adaptive-like. The cytokine profile then "belong to" picture is redundant, just name the cells and show their properties in a single cell rather than two.
The categorisation of the cells then based on their gamma chain is incorrect for human γδ T cells, this is a distinctly mouse specific categorisation and is misleading the reader. Human should only be delineated based on their delta chain usage.
2. Some inappropriate word choice used to explain things. Eg. Immune system “reactions” (line 42) “a comprehensive comprehension” (line 55), TCRs can “spot” lipid antigens (line 94), migratory “reactions” (line 130). Overall, the English of the article needs to be improved and appropriate scientific terminology needs to be better implemented.
3. Plasmodium falciparum should be italicised.
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