Abstract 16506: Increased Function of the CD28hi Phenotype Underlies the Reduction of Intimal Thickening by CD8+ T cells
Background: We recently reported that CD8+ T cells reduced intimal thickening after arterial injury with increased CD28 expression. Under basal conditions, CD28 is expressed by mouse CD8+ T cells (CD8+CD28+), but is upregulated in a sub-population on activation (CD8+CD28hi). In this study, we tested if this increased function of the CD8+CD28hi T cell phenotype after arterial injury is involved in the reduction of intimal thickening by CD8+ T cells.
Methods and Results: Peri-carotid arterial cuff injury was performed on wild type (WT) and CD4-/- mice. Splenic CD8+ T cells were collected at various time points after injury and co-cultured with syngeneic smooth muscle cells (SMC) at a T cell:SMC ratio of 3:1 in a 4 hour lytic assay. There was negligible lytic activity by CD8+ T cells from uninjured WT mice, which significantly increased 7 days after injury (Table). Depletion of CD28hi cells from WT CD8+ T cells 7 days after injury significantly reduced CD8+ lytic activity compared to non-depleted CD8+ T cells (0.6±0.2% vs. 2.1±0.2%, N=3 each; P<0.01). Interestingly, CD8+ T cells from uninjured CD4-/- mice had significant lytic activity which remained elevated 7 days after injury (Table). Thus, CD8+ T cells from uninjured CD4-/- mice had higher lytic activity compared to uninjured WT mice (Table). CD8+CD28hi T cells isolated from uninjured CD4-/- mice and adoptively transferred into recipient Rag-1-/- mice significantly reduced intimal thickening in the recipients compared to CD8+CD28+ T cell recipients and Rag-1-/- mice without adoptive cell transfer (1.4±0.5x10-2 mm2 vs. 1.9±0.3x10-2 mm2 and 2.1±0.8x10-2 mm2, respectively; N=8-10 each, P<0.05).
Conclusion: CD8+CD28hi T cells have increased cytolytic activity against SMC. Thus, our previously reported reduction in intimal thickening by CD8+ T cells can be attributed in part to increased function of the CD8+CD28hi phenotype.
- © 2012 by American Heart Association, Inc.