Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets
<p>Abstract</p> <p>Background</p> <p>It is well established that PD-1 is expressed by follicular T cells but its function in regulation of human T helper cells has been unclear. We investigated the expression modality and function of PD-1 expressed by human T cells spec...
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| Format: | Article |
| Language: | English |
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BMC
2011-09-01
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| Series: | BMC Immunology |
| Online Access: | http://www.biomedcentral.com/1471-2172/12/53 |
| _version_ | 1818448148596523008 |
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| author | Hillsamer Peter Kim Chang H Wang Chuanwu |
| author_facet | Hillsamer Peter Kim Chang H Wang Chuanwu |
| author_sort | Hillsamer Peter |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>It is well established that PD-1 is expressed by follicular T cells but its function in regulation of human T helper cells has been unclear. We investigated the expression modality and function of PD-1 expressed by human T cells specialized in helping B cells.</p> <p>Results</p> <p>We found that PD-1-expressing T cells are heterogeneous in PD-1 expression. We identified three different PD-1-expressing memory T cell subsets (i.e. PD-1<sup>low (+)</sup>, PD-1<sup>medium (++)</sup>, and PD-1<sup>high (+++) </sup>cells). PD-1<sup>+++ </sup>T cells expressed CXCR5 and CXCR4 and were localized in the rim of germinal centers. PD-1<sup>+ </sup>or PD-1<sup>++ </sup>cells expressed CCR7 and were present mainly in the T cell area or other parts of the B cell follicles. Utilizing a novel antigen density-dependent magnetic sorting (ADD-MS) method, we isolated the three T cell subsets for functional characterization. The germinal center-located PD-1<sup>+++ </sup>T cells were most efficient in helping B cells and in producing IL-21 and CXCL13. Other PD-1-expressing T cells, enriched with Th1 and Th17 cells, were less efficient than PD-1<sup>+++ </sup>T cells in these capacities. PD-1<sup>+++ </sup>T cells highly expressed Ki-67 and therefore appear active in cell activation and proliferation in vivo. IL-2 is a cytokine important for proliferation and survival of the PD-1<sup>+++ </sup>T cells. In contrast, IL-21, while a major effector cytokine produced by the PD-1-expressing T helper cells, had no function in generation, survival, or proliferation of the PD-1-expressing helper T cells at least in vitro. PD-1 triggering has a suppressive effect on the proliferation and B cell-helping function of PD-1<sup>+++ </sup>germinal center T cells.</p> <p>Conclusion</p> <p>Our results revealed the phenotype and effector function of PD-1-expressing T helper cell subsets and indicate that PD-1 restrains the B cell-helping function of germinal center-localized T cells to prevent excessive antibody response.</p> |
| first_indexed | 2024-12-14T20:14:55Z |
| format | Article |
| id | doaj.art-b69d4a98a246414cb109d514fff10f4f |
| institution | Directory Open Access Journal |
| issn | 1471-2172 |
| language | English |
| last_indexed | 2024-12-14T20:14:55Z |
| publishDate | 2011-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj.art-b69d4a98a246414cb109d514fff10f4f2022-12-21T22:48:52ZengBMCBMC Immunology1471-21722011-09-011215310.1186/1471-2172-12-53Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsetsHillsamer PeterKim Chang HWang Chuanwu<p>Abstract</p> <p>Background</p> <p>It is well established that PD-1 is expressed by follicular T cells but its function in regulation of human T helper cells has been unclear. We investigated the expression modality and function of PD-1 expressed by human T cells specialized in helping B cells.</p> <p>Results</p> <p>We found that PD-1-expressing T cells are heterogeneous in PD-1 expression. We identified three different PD-1-expressing memory T cell subsets (i.e. PD-1<sup>low (+)</sup>, PD-1<sup>medium (++)</sup>, and PD-1<sup>high (+++) </sup>cells). PD-1<sup>+++ </sup>T cells expressed CXCR5 and CXCR4 and were localized in the rim of germinal centers. PD-1<sup>+ </sup>or PD-1<sup>++ </sup>cells expressed CCR7 and were present mainly in the T cell area or other parts of the B cell follicles. Utilizing a novel antigen density-dependent magnetic sorting (ADD-MS) method, we isolated the three T cell subsets for functional characterization. The germinal center-located PD-1<sup>+++ </sup>T cells were most efficient in helping B cells and in producing IL-21 and CXCL13. Other PD-1-expressing T cells, enriched with Th1 and Th17 cells, were less efficient than PD-1<sup>+++ </sup>T cells in these capacities. PD-1<sup>+++ </sup>T cells highly expressed Ki-67 and therefore appear active in cell activation and proliferation in vivo. IL-2 is a cytokine important for proliferation and survival of the PD-1<sup>+++ </sup>T cells. In contrast, IL-21, while a major effector cytokine produced by the PD-1-expressing T helper cells, had no function in generation, survival, or proliferation of the PD-1-expressing helper T cells at least in vitro. PD-1 triggering has a suppressive effect on the proliferation and B cell-helping function of PD-1<sup>+++ </sup>germinal center T cells.</p> <p>Conclusion</p> <p>Our results revealed the phenotype and effector function of PD-1-expressing T helper cell subsets and indicate that PD-1 restrains the B cell-helping function of germinal center-localized T cells to prevent excessive antibody response.</p>http://www.biomedcentral.com/1471-2172/12/53 |
| spellingShingle | Hillsamer Peter Kim Chang H Wang Chuanwu Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets BMC Immunology |
| title | Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets |
| title_full | Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets |
| title_fullStr | Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets |
| title_full_unstemmed | Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets |
| title_short | Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets |
| title_sort | phenotype effector function and tissue localization of pd 1 expressing human follicular helper t cell subsets |
| url | http://www.biomedcentral.com/1471-2172/12/53 |
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