Abstract 1491: Selective and Specific Inhibitory Role of CD8+ T Cells in Intimal Thickening
Background: We have reported that arterial injury results in exuberant intimal thickening in immune-deficient Rag-1KO mice, which is inhibited by T cell transfer. We have also reported that CD4+ T cell deficiency (CD4KO) resulted in reduced intimal thickening compared to wild type and CD8+ T cell deficient mice (CD8KO). The role of specific T cell subpopulations was not clearly addressed because the CD4 and CD8 deficient mice have functional B cells that could modulate intimal thickening. To investigate the role of specific T cell subtypes without the confounding effects of B cell presence, we adoptively transferred T cells from CD4KO or CD8KO mice into Rag-1KO mice. We hypothesized that the CD8+ T cell population has a direct role in inhibiting intimal thickening.
Methods and Results: Rag-1KO mice were subjected to adoptive cell transfer of T cell-enriched splenocytes from CD4KO (CD8+T donor) or CD8KO (CD4+T donor) mice. Recipients were then subjected to carotid arterial cuff injury for 21 days. Controls were Rag-1KO mice without cell transfer. Intimal thickening in Rag-1KO mice was significantly reduced by CD8+ T cell transfer (2.0±0.9x10−2 vs. 1.2±0.8x10−2 mm2; p<0.05; n=9 each) but not by CD4+ T cell (1.8±0.9x10−2 mm2; n=7). Intima:media ratio was also significantly reduced in CD8+ T cell recipient mice (0.5±0.2 vs. 0.3±0.2; p<0.05). Real time-PCR of donor spleens suggested higher cytokine mRNA expression with a predominantly Th2 profile in the CD4+ donors. However, CD8+ recipient mice had increased cytokine expression compared to CD4+ recipients and control Rag-1KO mice 21 days after injury (Table 1⇓).
Conclusion: Our results confirm that T cell modulation of intimal thickening is selective and specific to CD8+ cells with a generalized increase in cytokine expression in Rag-1KO recipients. CD4+ cells do not appear to affect the response to injury.