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Arnholdt, Christoph; Kumaraswami, Konda; Goetz, Philipp; Kuebler, Matthias; Lasch, Manuel und Deindl, Elisabeth (2022): Depletion of gamma delta T Cells Leads to Reduced Angiogenesis and Increased Infiltration of Inflammatory M1-like Macrophages in Ischemic Muscle Tissue. In: Cells, Bd. 11, Nr. 9, 1490

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Abstract

gamma delta T cells, a small subset of T cells in blood, play a substantial role in influencing immunoregulatory and inflammatory processes. The functional impact of gamma delta T cells on angiogenesis in ischemic muscle tissue has never been reported and is the topic of the present work. Femoral artery ligation (FAL) was used to induce angiogenesis in the lower leg of gamma delta T cell depleted mice and wildtype and isotype antibody-treated control groups. Gastrocnemius muscle tissue was harvested 3 and 7 days after FAL and assessed using (immuno-)histological analyses. Hematoxylin and Eosin staining showed an increased area of tissue damage in gamma delta T cell depleted mice 7 days after FAL. Impaired angiogenesis was demonstrated by lower capillary to muscle fiber ratio and decreased number of proliferating endothelial cells (CD31(+) /BrdU(+)). gamma delta T cell depleted mice showed an increased number of total leukocytes (CD45(+)), neutrophils (MPO+) and neutrophil extracellular traps (NETs) (MPO+/CitH3(+)), without changes in the neutrophils to NETs ratio. Moreover, the depletion resulted in a higher macrophage count (DAPI/CD68(+)) caused by an increase in inflammatory M1-like macrophages (CD68(+)/MRC1(-)). Altogether, we show that depletion of gamma delta T cells leads to increased accumulation of leukocytes and M1-like macrophages, along with impaired angiogenesis.

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