Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T Cells
Unlike mice and humans, porcine γδ T cells represent a prominent subset of T cells in blood and secondary lymphatic organs. GATA-3, T-bet and Eomesodermin (Eomes) are transcription factors with crucial functions in T-cell development and functional differentiation, but their expression has not been...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.00396/full |
| _version_ | 1818303588354490368 |
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| author | Irene M. Rodríguez-Gómez Stephanie C. Talker Tobias Käser Maria Stadler Lisa Reiter Andrea Ladinig Jemma V. Milburn Jemma V. Milburn Sabine E. Hammer Kerstin H. Mair Kerstin H. Mair Armin Saalmüller Wilhelm Gerner Wilhelm Gerner |
| author_facet | Irene M. Rodríguez-Gómez Stephanie C. Talker Tobias Käser Maria Stadler Lisa Reiter Andrea Ladinig Jemma V. Milburn Jemma V. Milburn Sabine E. Hammer Kerstin H. Mair Kerstin H. Mair Armin Saalmüller Wilhelm Gerner Wilhelm Gerner |
| author_sort | Irene M. Rodríguez-Gómez |
| collection | DOAJ |
| description | Unlike mice and humans, porcine γδ T cells represent a prominent subset of T cells in blood and secondary lymphatic organs. GATA-3, T-bet and Eomesodermin (Eomes) are transcription factors with crucial functions in T-cell development and functional differentiation, but their expression has not been investigated in porcine γδ T cells so far. We analyzed the expression of these transcription factors in γδ thymocytes, mature γδ T cells from blood, spleen, lymph nodes, and lung tissue as well as in vitro stimulated γδ T cells on the protein level by flow cytometry. GATA-3 was present in more than 80% of all γδ-thymocytes. Extra-thymic CD2− γδ T cells expressed high levels of GATA-3 in all investigated organs and had a CD8α−/dimCD27+perforin− phenotype. T-bet expression was mainly found in a subset of CD2+ γδ T cells with an opposing CD8αhighCD27dim/−perforin+ phenotype. Eomes+ γδ T cells were also found within CD2+ γδ T cells but were heterogeneous in regard to expression of CD8α, CD27, and perforin. Eomes+ γδ T cells frequently co-expressed T-bet and dominated in the spleen. During aging, CD2−GATA-3+ γδ T cells strongly prevailed in young pigs up to an age of about 2 years but declined in older animals where CD2+T-bet+ γδ T cells became more prominent. Despite high GATA-3 expression levels, IL-4 production could not be found in γδ T cells by intracellular cytokine staining. Experiments with sorted and ConA + IL-2 + IL-12 + IL-18-stimulated CD2− γδ T cells showed that proliferating cells start expressing CD2 and T-bet, produce IFN-γ, but retain GATA-3 expression. In summary, our data suggest a role for GATA-3 in the development of γδ-thymocytes and in the function of peripheral CD2−CD8α−/dimCD27+perforin− γδ T cells. In contrast, T-bet expression appears to be restricted to terminal differentiation stages of CD2+ γδ T cells, frequently coinciding with perforin expression. The functional relevance of high GATA-3 expression levels in extra-thymic CD2− γδ T cells awaits further clarification. However, their unique phenotype suggests that they represent a thymus-derived separate lineage of γδ T cells in the pig for which currently no direct counterpart in rodents or humans has been described. |
| first_indexed | 2024-12-13T05:57:11Z |
| format | Article |
| id | doaj.art-883c4d1a00f5428ba9ef4f17a18d050d |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T05:57:11Z |
| publishDate | 2019-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-883c4d1a00f5428ba9ef4f17a18d050d2022-12-21T23:57:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-03-011010.3389/fimmu.2019.00396297382Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T CellsIrene M. Rodríguez-Gómez0Stephanie C. Talker1Tobias Käser2Maria Stadler3Lisa Reiter4Andrea Ladinig5Jemma V. Milburn6Jemma V. Milburn7Sabine E. Hammer8Kerstin H. Mair9Kerstin H. Mair10Armin Saalmüller11Wilhelm Gerner12Wilhelm Gerner13Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaUniversity Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Vienna, AustriaUniversity Clinic for Swine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaChristian Doppler Laboratory for Optimized Prediction of Vaccination Success in Pigs, Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaChristian Doppler Laboratory for Optimized Prediction of Vaccination Success in Pigs, Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaInstitute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaChristian Doppler Laboratory for Optimized Prediction of Vaccination Success in Pigs, Institute of Immunology, Department of Pathobiology, University of Veterinary Medicine Vienna, Vienna, AustriaUnlike mice and humans, porcine γδ T cells represent a prominent subset of T cells in blood and secondary lymphatic organs. GATA-3, T-bet and Eomesodermin (Eomes) are transcription factors with crucial functions in T-cell development and functional differentiation, but their expression has not been investigated in porcine γδ T cells so far. We analyzed the expression of these transcription factors in γδ thymocytes, mature γδ T cells from blood, spleen, lymph nodes, and lung tissue as well as in vitro stimulated γδ T cells on the protein level by flow cytometry. GATA-3 was present in more than 80% of all γδ-thymocytes. Extra-thymic CD2− γδ T cells expressed high levels of GATA-3 in all investigated organs and had a CD8α−/dimCD27+perforin− phenotype. T-bet expression was mainly found in a subset of CD2+ γδ T cells with an opposing CD8αhighCD27dim/−perforin+ phenotype. Eomes+ γδ T cells were also found within CD2+ γδ T cells but were heterogeneous in regard to expression of CD8α, CD27, and perforin. Eomes+ γδ T cells frequently co-expressed T-bet and dominated in the spleen. During aging, CD2−GATA-3+ γδ T cells strongly prevailed in young pigs up to an age of about 2 years but declined in older animals where CD2+T-bet+ γδ T cells became more prominent. Despite high GATA-3 expression levels, IL-4 production could not be found in γδ T cells by intracellular cytokine staining. Experiments with sorted and ConA + IL-2 + IL-12 + IL-18-stimulated CD2− γδ T cells showed that proliferating cells start expressing CD2 and T-bet, produce IFN-γ, but retain GATA-3 expression. In summary, our data suggest a role for GATA-3 in the development of γδ-thymocytes and in the function of peripheral CD2−CD8α−/dimCD27+perforin− γδ T cells. In contrast, T-bet expression appears to be restricted to terminal differentiation stages of CD2+ γδ T cells, frequently coinciding with perforin expression. The functional relevance of high GATA-3 expression levels in extra-thymic CD2− γδ T cells awaits further clarification. However, their unique phenotype suggests that they represent a thymus-derived separate lineage of γδ T cells in the pig for which currently no direct counterpart in rodents or humans has been described.https://www.frontiersin.org/article/10.3389/fimmu.2019.00396/fullγδ T cellsswinepigT-betEomesGATA-3 |
| spellingShingle | Irene M. Rodríguez-Gómez Stephanie C. Talker Tobias Käser Maria Stadler Lisa Reiter Andrea Ladinig Jemma V. Milburn Jemma V. Milburn Sabine E. Hammer Kerstin H. Mair Kerstin H. Mair Armin Saalmüller Wilhelm Gerner Wilhelm Gerner Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T Cells Frontiers in Immunology γδ T cells swine pig T-bet Eomes GATA-3 |
| title | Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T Cells |
| title_full | Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T Cells |
| title_fullStr | Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T Cells |
| title_full_unstemmed | Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T Cells |
| title_short | Expression of T-Bet, Eomesodermin, and GATA-3 Correlates With Distinct Phenotypes and Functional Properties in Porcine γδ T Cells |
| title_sort | expression of t bet eomesodermin and gata 3 correlates with distinct phenotypes and functional properties in porcine γδ t cells |
| topic | γδ T cells swine pig T-bet Eomes GATA-3 |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.00396/full |
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