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J Scott Hale

Publications and source records attributed to J Scott Hale.

3 recordsLinked to original sources

Guidelines for T cell nomenclature.

Advances in T cell biology have revealed heterogeneity among T cell populations that is not captured by existing general nomenclature. This issue has caused an ad hoc broadening of core T cell subset definitions and the invention of new subset designations that have not been uniformly delineated. To address this issue, in this Consensus Statement, we propose guidelines that serve three goals. First, they advocate that primary research reports define the experimental basis by which relevant subsets are designated in the methods section of each study. Second, they provide standardized definitions for existing subset designations in popular use, and common experimental criteria for defining each subset are noted. Last, they present an alternative 'modular nomenclature' paradigm. The newly proposed modular nomenclature eschews conceptualization of antigen-experienced T cells as belonging to a few idealized subsets, and the nomenclature instead simply indicates individual biological properties present in a T cell population with brief descriptors. Collectively, these guidelines intend to enhance transparency in the literature while facilitating clearer communication of findings and concepts to researchers, students and clinicians.

Terminology as Topic↗

Transcriptional control of Pactolus: evidence of a negative control region and comparison with its evolutionary paralogue, CD18 (beta2 integrin).

The mouse Pactolus and CD18 genes are highly conserved paralogues. The expression patterns of these genes are diverse in that most cells of hematopoietic lineage express CD18, but Pactolus is only expressed by maturing neutrophils. The minimal promoters of these two genes are homologous, including the conservation of two tandem PU.1-binding sites upstream of the transcriptional start site. To define the means by which these two structurally similar but functionally distinct promoters operate, a series of reporter assays, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation analyses, were performed. Transfection of Pactolus constructs into mouse macrophages, which do not express Pactolus, defined a negative control element within the first 100 base pairs. The presence of this negative regulatory site, distinct from the PU.1-binding site, was confirmed by EMSA oligonucleotide competition and gene reporter assays of Pactolus/CD18 chimeric constructs. Although PU.1 binding can be detected on Pactolus and CD18 minimal promoter segments with EMSA, only the CD18 promoter shows PU.1 binding in vivo, suggesting that the negative regulatory protein may block PU.1 from binding to the Pactolus promoter, thus inhibiting transcription of the gene. Sequence analysis of the negative control region in the Pactolus promoter suggested potential control by Snail and/or Smad families of transcription regulators. EMSA supershift analysis with antibodies against these proteins, using extracts from macrophages and mucosal mast cells, identified specific binding of Smuc to the promoter element, including a Smuc/PU.1/DNA trimeric complex. These data implicate Smuc as blocking Pactolus transcription in cells expressing PU.1 (and CD18) but not Pactolus.

Animals↗

Thymic output in aged mice.

Using GFP to mark recent thymic emigrants (RTEs) in mice carrying a GFP transgene driven by the recombination-activating gene 2 promoter, we demonstrate that RTEs are readily detectable even in 2-year-old mice, despite the fact that the proportion of the peripheral T cell pool comprised of RTEs declines with age. Although the number of RTEs decreases after reaching a peak at 6 weeks of age, thymic output as a function of thymic size is surprisingly age-independent. The CD4:CD8 ratio of RTEs declines with age, partly because of a striking decrease in steady-state proliferation of CD4+ RTEs in older mice. RTEs in aged mice undergo phenotypic maturation in the lymphoid periphery with delayed kinetics compared with young mice. RTEs from aged mice secrete less IL-2, proliferate less well, and achieve only weak expression of early-activation markers compared with more mature naïve peripheral T cells from the same mice. The proportion of GFP- cells in the CD4+ and CD8+ thymic compartments increases with age, partly as a result of leakiness in the aged thymus, allowing reentry of naïve peripheral T cells.

Aging↗