Effect of age and sex on immune checkpoint expression and kinetics in human T cellsReitsema, R. D., Hid Cadena, R., Nijhof, S. H., Abdulahad, W. H., Huitema, M. G., Paap, D., Brouwer, E., Boots, A. M. H. & Heeringa, P., 4-Nov-2020, In : Immunity & ageing : I & A. 17, 1, p. 1-12 12 p., 32.
Research output: Contribution to journal › Article › Academic › peer-review
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.
|Number of pages||12|
|Journal||Immunity & ageing : I & A|
|Publication status||Published - 4-Nov-2020|
- Immune checkpoints, Age, Sex, T cells, PD-1, CD40L, VISTA, CD28, GENDER, ARTHRITIS, LIGAND, LUPUS, CD40