Session Type: Poster Session (Sunday)
Session Time: 9:00AM-11:00AM
Background/Purpose: Giant cell arteritis (GCA) is the most frequent form of systemic vasculitis affecting the large- and medium-sized vessels. The involvement of innate immune cells and CD4+ T cells in the pathogenesis of GCA has been intensively studied. Interestingly, recent findings suggest a role of CD8+ T cells in disease development. However, CD8+ subsets and their functional capacities have not yet been studied in detail. Therefore, this study aims to investigate the phenotype and function of circulating CD8+ T cells in newly diagnosed GCA patients compared to healthy age- and sex- matched controls.
Methods: Newly diagnosed, untreated GCA patients (n=9), diagnosed according to international GCA consensus criteria, and age- and sex-matched healthy controls (HCs, n= 12) were enrolled. Firstly, peripheral blood mononuclear cells (PBMCs) were stained with fluorochrome-conjugated antibodies directed against CD3, CD4, CD8, CCR7, CD45RO, Ki-67, CD69 and CD25 and analyzed by flow cytometry. The following differentiation subsets were defined: CD8+ T naive (CD45RO-CCR7+), central memory (TCM, CD45RO+CCR7+), effector memory (TEM, CD45RO+CCR7-) and effector memory re-expressing CD45RA (TEMRA, CD45RO-CCR7-) cells. Secondly, the proliferative capacity of CD8+ T cells was determined in isolated CD3+ T cells by measuring the intensity of cell proliferation dye (CPD) upon 5 days of stimulation with plate-bound anti-CD3 or anti-CD3 plus soluble anti-CD28. Lastly, the proliferative capacity of whole blood sorted CD8+ T naive, TEM and TEMRA cells from two GCA patients in remission and two HCs was determined.
Results: No differences in the proportions of differentiation subsets were present between GCA patients and HCs. A proportional increase of Ki-67 within CD8+ TEM cells was found in GCA patients compared to HCs (p < 0.01) suggesting increased homeostatic proliferation in these cells. After stimulation with anti-CD3, the percentage of divided CD8+ T cells was higher in patients than in HCs (p< 0.05). After stimulation with both anti-CD3 and anti-CD28, no differences in proliferative capacity were found. Furthermore, a strong positive correlation between the proportion of CD8+ TEMRA cells and the percentage of divided cells upon CD3 stimulation was found in newly diagnosed GCA patients (R=0.8), and not in HCs. Preliminary data from sorted CD8+ differentiation subsets suggest that CD8+ TEMRA cells from GCA patients indeed have a higher proliferative capacity than those from HCs.
Conclusion: This study demonstrated that CD8+ TEM cells show increased homeostatic proliferation in GCA patients compared to HCs. Functional data on proliferative capacity suggest that CD8+ TEMRA cells from GCA patients are more rapidly activated by crosslinking CD3, suggesting either reduced regulation in these patients or more intrinsic threshold changes. This higher proliferative capacity of CD8+ TEMRA cells is contrary to existing literature, since it is well appreciated that the expansion potential of CD8+ T cells decreases from naive T cells to TCM to TEM and TEMRA. The lower activation thresholds for CD8+ TEMRA cells in GCA imply that these cells are not innocent bystanders but contribute to disease progression in GCA.
To cite this abstract in AMA style:Reitsema R, Hid Cadena R, Abdulahad W, Boots A, Heeringa P, Brouwer E. Elevated Proliferative Capacity of CD8+ T Cells in Giant Cell Arteritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/elevated-proliferative-capacity-of-cd8-t-cells-in-giant-cell-arteritis/. Accessed January 16, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-proliferative-capacity-of-cd8-t-cells-in-giant-cell-arteritis/