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...

Ful tanımlama

Detaylı Bibliyografya
Asıl Yazarlar: 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
Materyal Türü: Makale
Dil:English
Baskı/Yayın Bilgisi: BMC 2020-11-01
Seri Bilgileri:Immunity & Ageing
Konular:
Online Erişim:http://link.springer.com/article/10.1186/s12979-020-00203-y
_version_ 1828960997661999104
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
work_keys_str_mv AT rosannedreitsema effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells
AT rebecahidcadena effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells
AT sanderhnijhof effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells
AT wayelhabdulahad effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells
AT minkeghuitema effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells
AT davypaap effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells
AT elisabethbrouwer effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells
AT annemiekemhboots effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells
AT peterheeringa effectofageandsexonimmunecheckpointexpressionandkineticsinhumantcells