Human T-Cell Development and Thymic Egress: An Infectious Disease Perspective

Resop, Rachel S.; Uíttenbogaart, Christel H.

doi:10.1615/forumimmundisther.2015014226

Cited by 4 publications

(4 citation statements)

References 149 publications

(137 reference statements)

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“…This is noteworthy, as most studies addressing the expression of autoimmune risk genes investigate blood samples from adult individuals. An interesting instance is SIRPG, a gene associated with type 1 diabetes, which we have previously found to act an expression quantitative loci (eQTL) in human total thymic tissue [20]. Our current data revealed that SIRPG is particularly highly expressed the thymic CD8 + T cells, followed by the infant blood CD4 + and CD8 + T cells.…”

Section: Autoimmune Diseasesmentioning

confidence: 50%

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Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

Helgeland

Gabrielsen

Akselsen

et al. 2019

Preprint

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Background: The thymus is a highly specialized organ of the immune system where T cell precursors develop and differentiate into self-tolerant CD4+ or CD8+ T cells. No studies to date have investigated how the human transcriptome profiles differ, between T cells still residing in the thymus and T cells in the periphery.Results: We have performed high-throughput RNA sequencing to characterize the transcriptomes of primary single positive (SP) CD4+ and CD8+ T cells from infant thymic tissue, as well as primary CD4+ and CD8+ T cells from infant and adult peripheral blood, to enable the comparisons across tissues and ages. In addition, we have assessed the expression of candidate genes related to autoimmune diseases in thymic CD4+ and CD8+ T cells. Thymic SP T cells displayed a broader transcriptome than peripheral T cells, indicated by a higher number of uniquely expressed genes. Comparing T cells of thymic and blood origin, revealed more differentially expressed genes, than between infant and adult blood. Functional enrichment analysis revealed an over-representation of genes involved in cell cycle and replication in thymic T cells, whereas infant blood T cells were dominated by immune related terms. Comparing adult and infant blood T cells, the former was enriched for inflammatory response, cytokine production and biological adhesion, while upregulated genes in infant blood T cells were associated with cell cycle, cell death and gene expression.Conclusion: This study provides valuable insight into the transcriptomes of the human primary SP T cells still residing within the thymus, and offers a unique comparison to the more frequently studied primary blood derived T cells. We discovered that genes involved in migration, homing and recirculation, between peripheral blood and lymphatic tissue, were particularly active in infant blood T cells, suggesting active migration and recirculation in young children.

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Section: Autoimmune Diseasesmentioning

confidence: 50%

“…In mice, the T cell egress phenotype has been determined as Cd3 + Cd27 + Cd45ra + Cd62l + Cd69- (20). We found expression levels of SELL (CD62L) generally higher than CD69 in all samples, roughly two-fold, within each dataset (Fig.…”

Section: Markers Of Thymic Egressmentioning

confidence: 75%

Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

Helgeland

Gabrielsen

Akselsen

et al. 2019

Preprint

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show abstract

“…Tetramers can also be used to further focus the identification of TcR-specific cells in patients restricted to specific HLA alleles (e.g., HLA-A0201). The addition of markers, such as CD45RA, CCR7 and others, can be used to evaluate T-cell maturation states [59].…”

Section: Discussionmentioning

confidence: 99%

A Highly Sensitive Flow Cytometric Approach to Detect Rare Antigen-Specific T Cells: Development and Comparison to Standard Monitoring Tools

Levinsky

Brenner

Yalon

et al. 2023

Cancers

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Personalized vaccines against patient-unique tumor-associated antigens represent a promising new approach for cancer immunotherapy. Vaccine efficacy is assessed by quantification of changes in the frequency and/or the activity of antigen-specific T cells. Enzyme-linked immunosorbent spot (ELISpot) and flow cytometry (FCM) are methodologies frequently used for assessing vaccine efficacy. We tested these methodologies and found that both ELISpot and standard FCM [monitoring CD3/CD4/CD8/IFNγ/Viability+CD14+CD19 (dump)] demonstrate background IFNγ secretion, which, in many cases, was higher than the antigen-specific signal measured by the respective methodology (frequently ranging around 0.05–0.2%). To detect such weak T-cell responses, we developed an FCM panel that included two early activation markers, 4-1BB (CD137) and CD40L (CD154), in addition to the above-cited markers. These two activation markers have a close to zero background expression and are rapidly upregulated following antigen-specific activation. They enabled the quantification of rare T cells responding to antigens within the assay well. Background IFNγ-positive CD4 T cell frequencies decreased to 0.019% ± 0.028% and CD8 T cells to 0.009% ± 0.013%, which are 19 and 13 times lower, respectively, than without the use of these markers. The presented methodology enables highly sensitive monitoring of T-cell responses to tumor-associated antigens in the very low, but clinically relevant, frequencies.

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“…In mice, the T cell egress phenotype has been determined as Cd3 + Cd27 + Cd45ra + Cd62l + Cd69- [21]. In the thymus, CD69 expression has been reported to be downregulated in mature SP thymocytes, enabling expression of S1PR1 and egress from the thymus [22,23].…”

Section: T Cell Egress and Migrationmentioning

confidence: 99%

Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

et al. 2020

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Background: The thymus is a highly specialized organ of the immune system where T cell precursors develop and differentiate into self-tolerant CD4+ or CD8+ T cells. No studies to date have investigated how the human transcriptome profiles differ, between T cells still residing in the thymus and T cells in the periphery. Results: We have performed high-throughput RNA sequencing to characterize the transcriptomes of primary single positive (SP) CD4+ and CD8+ T cells from infant thymic tissue, as well as primary CD4+ and CD8+ T cells from infant and adult peripheral blood, to enable the comparisons across tissues and ages. In addition, we have assessed the expression of candidate genes related to autoimmune diseases in thymic CD4+ and CD8+ T cells. The thymic T cells showed the largest number of uniquely expressed genes, suggesting a more diverse transcription in thymic T cells. Comparing T cells of thymic and blood origin, revealed more differentially expressed genes, than between infant and adult blood. Functional enrichment analysis revealed an over-representation of genes involved in cell cycle and replication in thymic T cells, whereas infant blood T cells were dominated by immune related terms. Comparing adult and infant blood T cells, the former was enriched for inflammatory response, cytokine production and biological adhesion, while upregulated genes in infant blood T cells were associated with cell cycle, cell death and gene expression. Conclusion: This study provides valuable insight into the transcriptomes of the human primary SP T cells still residing within the thymus, and offers a unique comparison to primary blood derived T cells. Interestingly, the majority of autoimmune disease associated genes were expressed in one or more T cell subset, however~11% of these were not expressed in frequently studied adult peripheral blood.

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Human T-Cell Development and Thymic Egress: An Infectious Disease Perspective

Cited by 4 publications

References 149 publications

Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

A Highly Sensitive Flow Cytometric Approach to Detect Rare Antigen-Specific T Cells: Development and Comparison to Standard Monitoring Tools

Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

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