Elevated Proliferative Capacity of CD8+ T Cells in Giant Cell Arteritis

Rosanne Reitsema¹, Rebeca Hid Cadena ², Wayel Abdulahad ³, Annemieke Boots ³, Peter Heeringa ⁴ and Elisabeth Brouwer ¹, ¹Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, ²Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, ³Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, ⁴Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: CD8 cells and giant cell arteritis

Session Information

Date: Sunday, November 10, 2019

Session Title: T Cell Biology & Targets in Autoimmune & Inflammatory Disease Poster

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 (T_CM, CD45RO+CCR7+), effector memory (T_EM, CD45RO+CCR7-) and effector memory re-expressing CD45RA (T_EMRA, 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, T_EM and T_EMRA 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+ T_EM 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+ T_EMRA 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+ T_EMRA cells from GCA patients indeed have a higher proliferative capacity than those from HCs.

Conclusion: This study demonstrated that CD8+ T_EM cells show increased homeostatic proliferation in GCA patients compared to HCs. Functional data on proliferative capacity suggest that CD8+ T_EMRA 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+ T_EMRA 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 T_CM to T_EM and T_EMRA. The lower activation thresholds for CD8+ T_EMRA cells in GCA imply that these cells are not innocent bystanders but contribute to disease progression in GCA.

Disclosure: R. Reitsema, None; R. Hid Cadena, None; W. Abdulahad, None; A. Boots, Gruenenthal, 5; P. Heeringa, None; E. Brouwer, Roche, 5, 8.

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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