NTR: Early & Late cortical thymocyte

[avikdatta]

Label: CD3-negative, CD4-positive, CD8-positive, double positive thymocyte Synonyms: Early cortical thymocyte is_a: CL:0000809 ! double-positive, alpha-beta thymocyte Text definition: A double positive thymocyte with the phenotype CD3-negative, CD4-positive, CD8-positive Definition source: PMID: 12086890 (http://www.ncbi.nlm.nih.gov/pubmed/12086890)

Label: CD3-positive, CD4-positive, CD8-positive, double positive thymocyte Synonyms: Late cortical thymocyte is_a: CL:0000809 ! double-positive, alpha-beta thymocyte Text definition: A double positive thymocyte with the phenotype CD3-positive, CD4-positive, CD8-positive Definition source: PMID: 12086890 (http://www.ncbi.nlm.nih.gov/pubmed/12086890)

[avikdatta]

Hi,

Please let me know if any further details are required for adding these ontology terms.

thanks Avik

[addiehl]

Hi Avik,

Thank you for your term request, and sorry for the delay.

It seems you are basing your request on the schematic in Figure 3 of PMID:12086890. This figure is a representation of thymocyte development based presumably on multiple sources, though poorly referenced. None of the primary data for this figure is from this paper, and I suspect much of the understanding of thymocyte differentiation depicted in the figure is based on mouse data, although the paper itself is about human T cell acute lymphoblastic leukemia.

In looking at the first term you propose, I cannot use Figure 3 as evidence for this term, "CD3-negative, CD4-positive, CD8-positive, double positive thymocyte." Figure 3 shows a "CD3 -/low, CD4+, CD8+ early cortical thymocyte. A cell type cannot be both CD3-negative and CD3-low, which suggests that either more than one stage is being represented in the figure or that the authors are using CD3 -/low to indicate very low expression of CD3 in flow cytometry. This figure is not sufficient evidence that a CD3-negative (i.e. TCR negative) double positive thymocyte population exists. If you can find a primary source with evidence for a CD3-negative, double positive cell type, please let me know. The challenge is that CD3 is a component of the pre-TCR receptor containing a successfully recombined beta-chain and the invariant pre-TCR alpha chain, which is already present in the DN3/DN4 stage, and replaced by the alpha-beta TCR in the initial DP stage. So I am dubious that a CD3-negative DP-thymocyte actually exists.

Furthermore, the proposed cell type cannot be placed as a child of CL:0000809 ! double-positive, alpha-beta thymocyte. CL:0000809 ! double-positive, alpha-beta thymocyte is logically defined as having an 'alpha-beta T cell receptor complex', and 'alpha-beta T cell receptor complex' is a type of 'T cell receptor complex', and 'T cell receptor complex' is logically defined with has_part some 'CD3 episilon'. CD3 (CD3 epsilon) is used by immunologists as a proxy for the TCR, typically interpreted as the abTCR in most experimental contexts, so the CL:0000809 ! double-positive, alpha-beta thymocyte cell type necessarily bears CD3, as would any subtype.

In looking at your second term, CD3-positive, CD4-positive, CD8-positive, double positive thymocyte, in fact this term is already logically equivalent to its proposed parent term, CL:0000809 ! double-positive, alpha-beta thymocyte, per the logic in the previous paragraph, i.e. CL:0000809 already has_part CD3 epsilon, which a DL query in Protege verifies.

My solution for this second term is to add the broad synonym 'late cortical thymocyte' to CL:0000809. I will also add 'early cortical thymocyte' as a broad synonym to the CL terms for DN3 and DN4 (CL:0000807 and CL:0000808).

Sorry to be so negative, Alex

[addiehl]

Synonyms 'early cortical thymocyte' and 'late cortical thymocyte' added as described above.

[avikdatta]

Dear Alex,

Thanks for assigning these two cell types to the correct ontology terms.

regards Avik