Abstract 13488: Adoptive Transfer Experiments in ApoE-/- Mice Define an Inhibitory Role for CD8+CD25+ T Cells in Atherosclerosis
Background: CD4+ T cells are pro-atherogenic, yet adoptive transfer of the CD4+CD25+ T-regulatory sub-population reduces atherosclerosis. On the other hand, the role of CD8+ T cells in atherosclerosis remains to be explored. CD8+CD28+ T cells were recently reported to precede CD4+ T cell activation in response to an atherogenic diet. In this study, we investigated the role of another CD8+ T cell population, CD8+CD25+ in atherosclerosis.
Methods and Results: Seven week-old apoE-/- mice were fed an atherogenic diet or normal chow for 6 weeks and the percentage of peripheral blood CD8+CD25+ T cells was assessed. CD8+CD25+ T cells in atherogenic diet-fed mice was significantly decreased compared to that of normal chow-fed mice (1.9±0.8% vs 3.8±1.0%, respectively; N=5 each; P<0.05). CD8+CD25+ T cells were then isolated from spleens of 13 week-old naïve apoE-/- mice fed normal chow and adoptively transferred to 7 week-old apoE-/- recipient mice (1×105 cells per mouse) via the tail vein. PBS injected mice served as control. Mice were fed normal chow until 13 weeks of age and then changed to atherogenic diet until euthanasia at 25 weeks of age. En face aortic oil-red O stain showed that CD8+CD25+ T cell recipients had significantly reduced atherosclerosis compared to PBS (Table). CD8+CD62L+ cells were significantly reduced in the recipient mice (Table) suggesting increased memory cells. To determine if the reduction in atherosclerosis was simply due to increased CD8+ T cells by adoptive transfer, a higher number of total CD8+ T cells (1×106 per mouse) was injected into another group of recipient mice using the same schedule as in the first experiment. Injection of a higher number of unfractionated total CD8+ T cells had no effect on atherosclerosis.
Conclusion: Our data shows that CD8+CD25+ T cells down-modulated the development of atherosclerosis in apoE-/- mice. Lack of effect of total CD8+ T cell transfer suggests a function specific to the CD25+ sub-population of CD8+ T cells.
- © 2011 by American Heart Association, Inc.