The role of CD8+ Granzyme B+ T cells in the pathogenesis of Takayasu’s arteritis

• Published in: Clinical rheumatology 2022, Vol.41 (1), p.167-176
• Main Authors: Li, Taotao, Gao, Na, Cui, Wei, Zhao, Limin, Du, Juan, Shi, Xuemei, Zhu, Junming, Qiao, Zhiyu, Guo, Shichao, Pan, Lili
• Format: Article
• Language: English
• Subjects: Aorta; Arteritis; CD3 antigen; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes; Flow cytometry; Granzyme B; Granzymes; Humans; Immune response (cell-mediated); Immunofluorescence; Interferon-gamma; Lymphocytes; Lymphocytes T; Medicine; Medicine & Public Health; Original Article; Pathogenesis; Patients; Perforin; Rheumatology; T-Lymphocyte Subsets; Takayasu Arteritis; Takayasu's disease; Vein & artery diseases; γ-Interferon
• ISSN: 0770-3198; 1434-9949
• DOI: 10.1007/s10067-021-05903-4

Objective T cell-mediated immune response plays a key role in Takayasu arteritis (TAK) . Although previous studies have showed the roles of CD4 + T cell and its subsets in TAK, the change of CD8 + T cell subsets remains unclear. This study investigated the role of CD8 + T cell subsets in TAK. Methods The study consisted of 56 TA patients and 51 healthy controls. The percentages of CD8 + T cells, CD8 + GranzymeB + T cells, CD8 + Perforin + T cells, and CD8 + IFN-γ + T cells in blood samples were analyzed by flow cytometry. Results We found that the percentages of CD8 + GranzymeB + T cells ( P  = 0.030), CD8 + Perforin + T cells ( P  = 0.000), and CD8 + IFN-γ + T cells ( P  = 0.002) in CD8 + T cells were higher in TAK patients compared to control group. After 6 months of treatment, the proportion of CD8 + T cells in lymphocytes were significantly lower in TAK patients than the baseline assessment ( P  = 0.033). A lower ratio of CD8 + GranzymeB + T cells/CD8 + T cells were showed in TAK patents after treatment compared with TAK patients before treatments ( P  = 0.011). The change of CD8 + GranzymeB + T cells/CD8 + T cells ratio was positively correlated with the change of ITAS ( r  = 0.721, P  = 0.002) and ITAS-A ( r  = 0.637, P  = 0.008). Finally, the immunofluorescence staining showed the infiltration of CD8 + Granzyme B + cells in the aortic tissue of TAK patients. Conclusion Our results disclose that the CD8 + T lymphocytes may play a role in TAK pathogenesis. Targeting CD8 + GranzymeB + T lymphocytes or Granzyme B inhibitors could be a potential therapeutic approach for the treatment of TAK. Key Points • Our study investigated role the of CD8 + T cell subsets in TAK. • We found the percentages of CD8 + GranzymeB + T cells, CD8 + Perforin + T cells, and CD8 + IFN- γ + T cells in CD3 + CD8 + T cells were higher in TAK patients. • The proportion of CD8 + T cells in lymphocytes and the ratio of CD8 + GranzymeB + T cells/CD8 + T cells were significantly lower in TAK patients after treatment.