Background: Large vessel vasculitis comprises two distinct entities, giant cell arteritis (GCA) and Takayasu arteritis (TAK), which are clearly differentiated by the age of onset. While both diseases share clinical features associated with large vessel involvements, they exhibit differences in genetic background and comorbidities, suggesting the potential differences in their immunopathophysiology. Some studies have reported the involvement of cytotoxic CD4-positive T cells in the pathogenesis of GCA, whereas cytotoxic CD8-positive T cells have been implicated in TAK. However, no study has compared cytotoxic T cells between GCA and TAK.

Objectives: The study aimed to compare the involvement of cytotoxic T cell subsets between GCA and TAK, especially focusing on CX3CR1-positive T cells which are known for their specific production of cytotoxic molecules such as granzyme B and perforin.

Methods: We enrolled treatment-naïve 30 patients with active large vessel vasculitis (GCA, n=22 and TAK, n=8) and 16 healthy controls in the study and collected fresh blood samples before and after immunosuppressive treatment. Using flow cytometry, we compared the proportions of CX3CR1-positive CD4 T cells and CX3CR1-positive CD8 T cells in their peripheral blood. Additionally, we conducted correlation analyses between these T cell subsets and clinical indicators. Furthermore, tissue sections from the affected arterial lesions obtained from some patients were assessed for the infiltration of CX3CR1-positive T cells using immunohistochemical staining. Lastly, we performed a longitudinal analysis of CX3CR1-positive T cells over a period of three months after the initiation of immunosuppressive treatment.

Results: We found an increased proportion of CX3CR1-positive CD4 T cells in peripheral blood in GCA compared to healthy controls, whereas there was no significant change in TAK. Unexpectedly, no differences were found in the proportion of CX3CR1-positive CD8 T cells in peripheral blood among GCA, TAK, and healthy controls. Furthermore, the increased proportion of CX3CR1-positive CD4 T cells strongly correlated with the severity of inflammatory markers and anemia only in patients with GCA, while there was no significant correlation between CX3CR1-positive T cells and inflammation parameters in patients with TAK. Biopsy samples of the affected temporal artery from GCA patients revealed infiltration of numerous CX3CR1-positive T cells from the adventitia to the media and intima, leading to inflammation, disruption of the internal and external elastic lamina and intimal hyperplasia. Longitudinal analysis after immunosuppressive treatment showed a reduction in the proportion of CX3CR1-positive T cells in the blood, accompanied by the attenuation of disease activity in GCA patients. On the other hand, no significant changes were observed in the proportion of CX3CR1-positive T cells in TAK patients.

Conclusion: Our findings suggest distinct immunopathogenic mechanisms between GCA and TAK. In GCA, cytotoxic CX3CR1-positive T cells were implicated in systemic inflammation and the inflammatory destruction as well as remodeling of large vessels, which may be potential treatment target for GCA.

REFERENCES: [1] Li T, Gao N, Cui W, Zhao L, Du J, Shi X, et al. The role of CD8+ Granzyme B+ T cells in the pathogenesis of Takayasu’s arteritis. Clin Rheumatol. 2022;41:167-176.

[2] Carmona EG, Callejas-Rubio JL, Raya E, Ríos-Fernández R, Villanueva-Martín G, Cid MC, et al. Single-cell transcriptomic profiling reveals a pathogenic role of cytotoxic CD4+ T cells in giant cell arteritis. J Autoimmun. 2023;142:103124.

Acknowledgements: NIL.

Disclosure of Interests: None declared.