Effect of age and sex on immune checkpoint expression and kinetics in human T cells
Abstract Background Immune checkpoints are crucial molecules in maintaining a proper immune balance. Even though age and sex are known to have effects on the immune system, the interplay between age, sex and immune checkpoint expression by T cells is not known. The aim of this study was to determine...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-11-01
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| Series: | Immunity & Ageing |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12979-020-00203-y |
| _version_ | 1828960997661999104 |
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| author | Rosanne D. Reitsema Rebeca Hid Cadena Sander H. Nijhof Wayel H. Abdulahad Minke G. Huitema Davy Paap Elisabeth Brouwer Annemieke M. H. Boots Peter Heeringa |
| author_facet | Rosanne D. Reitsema Rebeca Hid Cadena Sander H. Nijhof Wayel H. Abdulahad Minke G. Huitema Davy Paap Elisabeth Brouwer Annemieke M. H. Boots Peter Heeringa |
| author_sort | Rosanne D. Reitsema |
| collection | DOAJ |
| description | Abstract Background Immune checkpoints are crucial molecules in maintaining a proper immune balance. Even though age and sex are known to have effects on the immune system, the interplay between age, sex and immune checkpoint expression by T cells is not known. The aim of this study was to determine whether age and sex affect immune checkpoint expression by T cells and if age and sex affect the kinetics of immune checkpoint expression following ex vivo stimulation. In this study, whole blood samples of 20 healthy young adults (YA, 9 males and 11 females) and 20 healthy older adults (OA, 9 males and 11 females) were stained for lymphocyte lineage markers and immune checkpoints and frequencies of CD28+, PD-1+, VISTA+ and CD40L+ T cells were determined. Immune checkpoint expression kinetics were studied following ex vivo anti-CD3/anti-CD28 stimulation of T cells from young and older healthy adults. Results We report an age-associated increase of CD40L + CD4+ and CD40L + CD8+ T-cell frequencies, whereas CD40+ B-cell frequencies were decreased in older adults, suggesting modulation of the CD40L-CD40 interaction with age. Immune checkpoint expression kinetics revealed differences in magnitude between CD4+ and CD8+ T cells independent of age and sex. Further analysis of CD4+ T-cell subsets revealed an age-associated decrease of especially PD-1 + CD4+ memory T cells which tracked with the female sex. Conclusion Collectively, our results demonstrate that both age and sex modulate expression of immune checkpoints by human T cells. These findings may have implications for optimising vaccination and immune checkpoint immunotherapy and move the field towards precision medicine in the management of older patient groups. |
| first_indexed | 2024-12-14T09:38:26Z |
| format | Article |
| id | doaj.art-ea3b52e7c6084c55b0d18f6d05e3bb5c |
| institution | Directory Open Access Journal |
| issn | 1742-4933 |
| language | English |
| last_indexed | 2024-12-14T09:38:26Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Immunity & Ageing |
| spelling | doaj.art-ea3b52e7c6084c55b0d18f6d05e3bb5c2022-12-21T23:07:52ZengBMCImmunity & Ageing1742-49332020-11-0117111210.1186/s12979-020-00203-yEffect of age and sex on immune checkpoint expression and kinetics in human T cellsRosanne D. Reitsema0Rebeca Hid Cadena1Sander H. Nijhof2Wayel H. Abdulahad3Minke G. Huitema4Davy Paap5Elisabeth Brouwer6Annemieke M. H. Boots7Peter Heeringa8Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center GroningenDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center GroningenDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center GroningenDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center GroningenDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center GroningenDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center GroningenDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center GroningenDepartment of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center GroningenDepartment of Pathology and Medical Biology, University of Groningen, University Medical Center GroningenAbstract Background Immune checkpoints are crucial molecules in maintaining a proper immune balance. Even though age and sex are known to have effects on the immune system, the interplay between age, sex and immune checkpoint expression by T cells is not known. The aim of this study was to determine whether age and sex affect immune checkpoint expression by T cells and if age and sex affect the kinetics of immune checkpoint expression following ex vivo stimulation. In this study, whole blood samples of 20 healthy young adults (YA, 9 males and 11 females) and 20 healthy older adults (OA, 9 males and 11 females) were stained for lymphocyte lineage markers and immune checkpoints and frequencies of CD28+, PD-1+, VISTA+ and CD40L+ T cells were determined. Immune checkpoint expression kinetics were studied following ex vivo anti-CD3/anti-CD28 stimulation of T cells from young and older healthy adults. Results We report an age-associated increase of CD40L + CD4+ and CD40L + CD8+ T-cell frequencies, whereas CD40+ B-cell frequencies were decreased in older adults, suggesting modulation of the CD40L-CD40 interaction with age. Immune checkpoint expression kinetics revealed differences in magnitude between CD4+ and CD8+ T cells independent of age and sex. Further analysis of CD4+ T-cell subsets revealed an age-associated decrease of especially PD-1 + CD4+ memory T cells which tracked with the female sex. Conclusion Collectively, our results demonstrate that both age and sex modulate expression of immune checkpoints by human T cells. These findings may have implications for optimising vaccination and immune checkpoint immunotherapy and move the field towards precision medicine in the management of older patient groups.http://link.springer.com/article/10.1186/s12979-020-00203-yImmune checkpointsAgeSexT cellsPD-1CD40L |
| spellingShingle | Rosanne D. Reitsema Rebeca Hid Cadena Sander H. Nijhof Wayel H. Abdulahad Minke G. Huitema Davy Paap Elisabeth Brouwer Annemieke M. H. Boots Peter Heeringa Effect of age and sex on immune checkpoint expression and kinetics in human T cells Immunity & Ageing Immune checkpoints Age Sex T cells PD-1 CD40L |
| title | Effect of age and sex on immune checkpoint expression and kinetics in human T cells |
| title_full | Effect of age and sex on immune checkpoint expression and kinetics in human T cells |
| title_fullStr | Effect of age and sex on immune checkpoint expression and kinetics in human T cells |
| title_full_unstemmed | Effect of age and sex on immune checkpoint expression and kinetics in human T cells |
| title_short | Effect of age and sex on immune checkpoint expression and kinetics in human T cells |
| title_sort | effect of age and sex on immune checkpoint expression and kinetics in human t cells |
| topic | Immune checkpoints Age Sex T cells PD-1 CD40L |
| url | http://link.springer.com/article/10.1186/s12979-020-00203-y |
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