Regression of atherosclerosis with anti-CD3 antibody via augmenting a regulatory T-cell response in mice

T Kita, T Yamashita, N Sasaki, K Kasahara… - Cardiovascular …, 2014 - academic.oup.com
T Kita, T Yamashita, N Sasaki, K Kasahara, Y Sasaki, K Yodoi, M Takeda, K Nakajima…
Cardiovascular research, 2014academic.oup.com
Aims Although recent animal studies have investigated the cellular and molecular
mechanisms underlying the process of atherosclerosis regression, it remains unknown
whether adaptive immune responses including T cells are involved in this process. We
investigated the role of T cells in atherosclerosis regression. Methods and results LDL
receptor-deficient mice were fed a high-cholesterol diet for 8 weeks to form atherosclerotic
lesions and were then changed to a standard diet, and atherosclerosis was assessed 4 …
Aims
Although recent animal studies have investigated the cellular and molecular mechanisms underlying the process of atherosclerosis regression, it remains unknown whether adaptive immune responses including T cells are involved in this process. We investigated the role of T cells in atherosclerosis regression.
Methods and results
LDL receptor-deficient mice were fed a high-cholesterol diet for 8 weeks to form atherosclerotic lesions and were then changed to a standard diet, and atherosclerosis was assessed 4 weeks later. Just before changing the diet, the mice received an iv injection of anti-CD3 antibody (CD3-Ab) or control immunoglobulin G for 5 consecutive days. CD3-Ab treatment regressed atherosclerosis and decreased the accumulation of macrophages and CD4+ T cells in the plaques. CD3-Ab treatment also dramatically reduced CD4+ T cells and increased the proportion of regulatory T cells (Tregs). Depletion of Tregs by anti-CD25 antibody injection abolished the regression of atherosclerosis seen in CD3-Ab-treated mice, indicating the essential role for Tregs in this process.
Conclusion
CD3-Ab treatment induced rapid regression of established atherosclerosis via reducing CD4+ T cells and increasing the proportion of Tregs. These findings suggest that therapeutic intervention for T-cell-mediated immune responses may represent a novel strategy to induce atherosclerosis regression in combination with lipid-lowering therapy.
Oxford University Press