10.1093/rheumatology/keac250
https://zenodo.org/records/6630283
oai:zenodo.org:6630283
Reitsema, Rosanne D.
Rosanne D.
Reitsema
0000-0002-4250-0930
van der Geest, Kornelis S. M.
Kornelis S. M.
van der Geest
0000-0003-2798-6765
Sandovici, Maria
Maria
Sandovici
Jiemy, William F.
William F.
Jiemy
Graver, Jacoba C.
Jacoba C.
Graver
Abdulahad, Wayel H.
Wayel H.
Abdulahad
Boots, Annemieke M.H.
Annemieke M.H.
Boots
Herringa, Peter
Peter
Herringa
0000-0001-8684-763X
Brouwer, Elisabeth
Elisabeth
Brouwer
Phenotypic, transcriptomic and functional profiling reveal reduced activation thresholds of CD81 T cells in giant cell arteritis
Zenodo
2022
GCA
vasculitis
T-cells
single-cell RNA sequencing
CD8+ T cells
2022-04-23
eng
https://zenodo.org/communities/immune-image
https://zenodo.org/communities/eu
Creative Commons Attribution 4.0 International
Objectives. Evidence from temporal artery tissue and blood suggests involvement of CD8þ T cells in the pathogenesis of GCA, but their exact role is poorly understood. Therefore, we performed a comprehensive analysis of circulating and lesional CD8þ T cells in GCA patients.
Methods. Circulating CD8þ T cells were analysed for differentiation status (CD45RO, CCR7), markers of activation (CD69 and CD25) and proliferation (Ki-67) in 14 newly diagnosed GCA patients and 18 healthy controls by flow cytometry. Proliferative capacity of CD8þ T cells upon anti-CD3 and anti-CD3/28 in vitro stimulation was assessed. Single-cell RNA sequencing of peripheral blood mononuclear cells of patients and controls (n¼3 each) was performed for mechanistic insight. Immunohistochemistry was used to detect CD3, CD8, Ki-67, TNF-a and IFN-c in GCA-affected tissues.
Results. GCA patients had decreased numbers of circulating effector memory CD8þ T cells but the percentage of Ki-67-expressing effector memory CD8þ T cells was increased. Circulating CD8þ T cells from GCA patients demonstrated reduced T cell receptor activation thresholds and displayed a gene expression profile that is concurrent with increased proliferation. CD8þ T cells were detected in GCA temporal arteries and aorta. These vascular CD8þ T cells expressed IFN-c but not Ki-67.
Conclusion. In GCA, circulating effector memory CD8þ T cells demonstrate a proliferation-prone phenotype. The presence of CD8þ T cells in inflamed arteries seems to reflect recruitment of circulating cells rather than local expansion. CD8þ T cells in inflamed tissues produce IFN-c, which is an important mediator of local inflammatory responses in GCA.
European Commission
10.13039/501100000780
831514
Immune-Image: Specific Imaging of Immune Cell Dynamics Using Novel Tracer Strategies