CD8+ T Cells Promote Pathological Angiogenesis in Ocular Neovascular Disease

Deliyanti, D; Figgett, WA; Gebhardt, T; Trapani, JA; Mackay, F; Wilkinson-Berka, JL

Author(s): Deliyanti, D; Figgett, WA; Gebhardt, T; Trapani, JA; Mackay, F; Wilkinson-Berka, JL;
Details: Publication Year 2023-04,Volume 43,Issue #4,Page 522-536
Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology
Publication Type: Research article
Abstract: BACKGROUND: CD4(+) (cluster of differentation) and CD8(+) T cells are increased in the ocular fluids of patients with neovascular retinopathy, yet their role in the disease process is unknown. METHODS: We describe how CD8(+) T cells migrate into the retina and contribute to pathological angiogenesis by releasing cytokines and cytotoxic factors. RESULTS: In oxygen-induced retinopathy, flow cytometry revealed the numbers of CD4(+) and CD8(+) T cells were increased in blood, lymphoid organs, and retina throughout the development of neovascular retinopathy. Interestingly, the depletion of CD8(+) T cells but not CD4(+) T cells reduced retinal neovascularization and vascular leakage. Using reporter mice expressing gfp (green fluorescence protein) in CD8(+) T cells, these cells were localized near neovascular tufts in the retina, confirming that CD8(+) T cells contribute to the disease. Furthermore, the adoptive transfer of CD8(+) T cells deficient in TNF (tumor necrosis factor), IFNgamma (interferon gamma), Prf (perforin), or GzmA/B (granzymes A/B) into immunocompetent Rag1(-/-) mice revealed that CD8(+) T cells mediate retinal vascular disease via these factors, with TNF influencing all aspects of vascular pathology. The pathway by which CD8(+) T cells migrate into the retina was identified as CXCR3 (C-X-C motif chemokine receptor 3) with the CXCR3 blockade reducing the number of CD8(+) T cells within the retina and retinal vascular disease. CONCLUSIONS: We discovered that CXCR3 is central to the migration of CD8(+) T cells into the retina as the CXCR3 blockade reduced the number of CD8(+) T cells within the retina and vasculopathy. This research identified an unappreciated role for CD8(+) T cells in retinal inflammation and vascular disease. Reducing CD8(+) T cells via their inflammatory and recruitment pathways is a potential treatment for neovascular retinopathies.
Publisher: Lippincott Williams & Wilkins
Keywords: Animals; Mice; CD8-Positive T-Lymphocytes/metabolism; Neovascularization, Pathologic; Retina/metabolism; *Retinal Diseases/metabolism; Interferon-gamma/metabolism; *Vascular Diseases/pathology; Mice, Inbred C57BL; flow cytometry; granzymes; perforin; retinal neovascularization
Department(s): Laboratory Research
PubMed ID: 36794587
Publisher's Version: https://doi.org/10.1161/ATVBAHA.122.318079
Open Access at Publisher's Site: https://doi.org/10.1161/atvbaha.122.318079
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-04-06 06:53:44

Last Modified: 2023-04-17 11:52:08