Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses
Extracellular vesicles (EVs) are known to contain unique proteins that reflect the cells of origins. Activated T cells are reported to secrete various EVs. To establish T cell subset-specific biomarkers, we performed proteomic analysis with Th1- and Th2-derived EVs and identified HLA-DR as a Th1-dom...
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| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2019/6720819 |
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| author | Ryutaro Oba Motomichi Isomura Akira Igarashi Kinya Nagata |
| author_facet | Ryutaro Oba Motomichi Isomura Akira Igarashi Kinya Nagata |
| author_sort | Ryutaro Oba |
| collection | DOAJ |
| description | Extracellular vesicles (EVs) are known to contain unique proteins that reflect the cells of origins. Activated T cells are reported to secrete various EVs. To establish T cell subset-specific biomarkers, we performed proteomic analysis with Th1- and Th2-derived EVs and identified HLA-DR as a Th1-dominated EV membrane protein. We designed a measurement system for CD3+CD4+, CD3+CD8+, and CD3+HLA-DR+ EVs to specifically determine EV subpopulations derived from CD4+, CD8+, and Th1-type T cells, respectively. In vitro analysis showed that CD3+CD4+ EVs and CD3+CD8+ EVs were selectively secreted from activated CD4+ and CD8+ T cells, respectively, and that CD3+HLA-DR+ EVs were actively secreted from not only Th1 but also activated CD8+ T (probably mostly Tc1) cells. To evaluate the clinical usefulness of these EVs, we measured the serum levels in patients with inflammatory diseases, including Epstein-Barr virus (EBV, n=13) infection, atopic dermatitis (AD, n=10), rheumatoid arthritis (RA, n=20), and osteoarthritis (OA, n=20) and compared the levels with those of healthy adults (n=20). CD3+CD4+ EVs were significantly higher in all of EBV infection, AD, RA, and OA while CD3+CD8+ EVs were higher in EBV infection, lower in RA, and not different in AD and OA relative to the control. The levels of CD3+HLA-DR+ EVs were markedly higher in EBV infection and significantly lower in AD. The results suggest that these EV subpopulations reflect in vivo activation status of total CD4+, total CD8+, and Th1/Tc1-type T cells, respectively, and may be helpful in T cell-related clinical settings, such as cancer immunotherapy and treatment of chronic infection, autoimmune diseases, and graft-versus-host disease. |
| format | Article |
| id | doaj-art-644f7bfa2da44fbd8d3aee09312846b9 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-644f7bfa2da44fbd8d3aee09312846b92025-02-03T01:26:09ZengWileyJournal of Immunology Research2314-88612314-71562019-01-01201910.1155/2019/67208196720819Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune ResponsesRyutaro Oba0Motomichi Isomura1Akira Igarashi2Kinya Nagata3Division of Advanced Technology and Development, BML Inc., Saitama, JapanDivision of Advanced Technology and Development, BML Inc., Saitama, JapanDivision of Advanced Technology and Development, BML Inc., Saitama, JapanDivision of Advanced Technology and Development, BML Inc., Saitama, JapanExtracellular vesicles (EVs) are known to contain unique proteins that reflect the cells of origins. Activated T cells are reported to secrete various EVs. To establish T cell subset-specific biomarkers, we performed proteomic analysis with Th1- and Th2-derived EVs and identified HLA-DR as a Th1-dominated EV membrane protein. We designed a measurement system for CD3+CD4+, CD3+CD8+, and CD3+HLA-DR+ EVs to specifically determine EV subpopulations derived from CD4+, CD8+, and Th1-type T cells, respectively. In vitro analysis showed that CD3+CD4+ EVs and CD3+CD8+ EVs were selectively secreted from activated CD4+ and CD8+ T cells, respectively, and that CD3+HLA-DR+ EVs were actively secreted from not only Th1 but also activated CD8+ T (probably mostly Tc1) cells. To evaluate the clinical usefulness of these EVs, we measured the serum levels in patients with inflammatory diseases, including Epstein-Barr virus (EBV, n=13) infection, atopic dermatitis (AD, n=10), rheumatoid arthritis (RA, n=20), and osteoarthritis (OA, n=20) and compared the levels with those of healthy adults (n=20). CD3+CD4+ EVs were significantly higher in all of EBV infection, AD, RA, and OA while CD3+CD8+ EVs were higher in EBV infection, lower in RA, and not different in AD and OA relative to the control. The levels of CD3+HLA-DR+ EVs were markedly higher in EBV infection and significantly lower in AD. The results suggest that these EV subpopulations reflect in vivo activation status of total CD4+, total CD8+, and Th1/Tc1-type T cells, respectively, and may be helpful in T cell-related clinical settings, such as cancer immunotherapy and treatment of chronic infection, autoimmune diseases, and graft-versus-host disease.http://dx.doi.org/10.1155/2019/6720819 |
| spellingShingle | Ryutaro Oba Motomichi Isomura Akira Igarashi Kinya Nagata Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses Journal of Immunology Research |
| title | Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses |
| title_full | Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses |
| title_fullStr | Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses |
| title_full_unstemmed | Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses |
| title_short | Circulating CD3+HLA-DR+ Extracellular Vesicles as a Marker for Th1/Tc1-Type Immune Responses |
| title_sort | circulating cd3 hla dr extracellular vesicles as a marker for th1 tc1 type immune responses |
| url | http://dx.doi.org/10.1155/2019/6720819 |
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