Article thumbnail

Enhanced Neointima Formation Following Arterial Injury in Immune Deficient Rag-1−/− Mice Is Attenuated by Adoptive Transfer of CD8+ T cells

By Paul C. Dimayuga, Kuang-Yuh Chyu, Jonathan Kirzner, Juliana Yano, Xiaoning Zhao, Jianchang Zhou, Prediman K. Shah and Bojan Cercek

Abstract

T cells modulate neointima formation after arterial injury but the specific T cell population that is activated in response to arterial injury remains unknown. The objective of the study was to identify the T cell populations that are activated and modulate neointimal thickening after arterial injury in mice. Arterial injury in wild type C57Bl6 mice resulted in T cell activation characterized by increased CD4+CD44hi and CD8+CD44hi T cells in the lymph nodes and spleens. Splenic CD8+CD25+ T cells and CD8+CD28+ T cells, but not CD4+CD25+ and CD4+CD28+ T cells, were also significantly increased. Adoptive cell transfer of CD4+ or CD8+ T cells from donor CD8−/− or CD4−/− mice, respectively, to immune-deficient Rag-1−/− mice was performed to determine the T cell subtype that inhibits neointima formation after arterial injury. Rag-1−/− mice that received CD8+ T cells had significantly reduced neointima formation compared with Rag-1−/− mice without cell transfer. CD4+ T cell transfer did not reduce neointima formation. CD8+ T cells from CD4−/− mice had cytotoxic activity against syngeneic smooth muscle cells in vitro. The study shows that although both CD8+ T cells and CD4+ T cells are activated in response to arterial injury, adoptive cell transfer identifies CD8+ T cells as the specific and selective cell type involved in inhibiting neointima formation

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3101237
Provided by: PubMed Central

To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.

Suggested articles

Citations

  1. (2003). [Late T-lymphocyte and monocyte activation in coronary restenosis. Evidence for a persistent inflammatory/immune mechanism?].
  2. (2001). A novel flow cytometric assay for quantitation and multiparametric characterization of cellmediated cytotoxicity.
  3. (2001). Absence of CD40 signaling is associated with an increase in intimal thickening after arterial injury.
  4. (2005). Altered trafficking of CD8+ memory T cells after implantation of rapamycin-eluting stents in patients with coronary artery disease.
  5. (1985). Autoimmune vasculitis resulting from in vitro immunization of lymphocytes to smooth muscle.
  6. (2007). Biological effects of drug-eluting stents in the coronary circulation.
  7. (2002). Both apolipoprotein E and immune deficiency exacerbate neointimal hyperplasia after vascular injury in mice.
  8. (1990). CD28 is an inducible T cell surface antigen that transduces a proliferative signal in CD3+ mature thymocytes.
  9. (1994). CD4+ mononuclear cells induce cytokine expression, vascular smooth muscle cell proliferation, and arterial occlusion after endothelial injury.
  10. (2000). Cell injury releases endogenous adjuvants that stimulate cytotoxic T cell responses.
  11. (2006). Central role of endogenous Toll-like receptor-2 activation in regulating inflammation, reactive oxygen species production, and subsequent neointimal formation after vascular injury.
  12. (2004). Comparison of frequency of interferon-gamma-positive CD4+ T cells before and after percutaneous coronary intervention and the effect of statin therapy in patients with stable angina pectoris.
  13. (2006). Cutting edge: hypoxia-inducible factor 1alpha and its activation-inducible short isoform I.1 negatively regulate functions of CD4+ and CD8+ T lymphocytes.
  14. (1999). Decreased neointimal thickening after arterial wall injury in inducible nitric oxide synthase knockout mice.
  15. (2006). Deficiency in CCR5 but not CCR1 protects against neointima formation in atherosclerosis-prone mice: involvement of IL-10.
  16. (2001). Differential regulation of two alternatively spliced isoforms of hypoxia-inducible factor-1 alpha in activated T lymphocytes.
  17. (2007). Expression of HIF-1alpha in injured arteries controls SDF-1alpha mediated neointima formation in apolipoprotein E deficient mice.
  18. (1993). General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia.
  19. (2002). Heatshock proteins as activators of the innate immune system.
  20. (1999). Homeostatic expansion and phenotypic conversion of naive T cells in response to self peptide/MHC ligands.
  21. (2011). Hypoxia and inflammation.
  22. (2007). Hypoxia inducible factor (HIF)-1 coordinates induction of Toll-like receptors TLR2 and TLR6 during hypoxia.
  23. (2010). Immune responses regulating the response to vascular injury.
  24. (2002). Inhibitory effect on arterial injury-induced neointimal formation by adoptive Bcell transfer in Rag-1 knockout mice.
  25. (2007). Innate and adaptive immune response to apoptotic cells.
  26. (2007). Involvement of the CD1d-natural killer T cell pathway in neointima formation after vascular injury.
  27. (2000). Naive T cells transiently acquire a memory-like phenotype during homeostasis-driven proliferation.
  28. (2009). Natural antibodies and complement modulate intimal thickening after arterial injury.
  29. (2000). Nonhypoxic pathway mediates the induction of hypoxia-inducible factor 1alpha in vascular smooth muscle cells.
  30. (1992). RAG-1-deficient mice have no mature B and T lymphocytes.
  31. (1997). Requirement for CD44 in activated T cell extravasation into an inflammatory site.
  32. (2010). Role of hypoxiainducible factor 1alpha in T cells as a negative regulator in development of vascular remodeling.
  33. (2010). Stat3-dependent acute Rantes production in vascular smooth muscle cells modulates inflammation following arterial injury in mice.
  34. (2005). T cell modulation of intimal thickening after vascular injury: the bimodal role of IFNgamma in immune deficiency.
  35. (1991). T lymphocytes inhibit the vascular response to injury.
  36. (2008). Th2-dependent cytokine release in patients treated with coronary angioplasty.
  37. (2004). The CD8 population in CD4-deficient mice is heavily contaminated with MHC class II-restricted T cells.
  38. (2003). The main function of IL-2 is to promote the development of T regulatory cells.
  39. (2005). Toll-like receptor 2 stimulation induces intimal hyperplasia and atherosclerotic lesion development.
  40. (2000). Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice.
  41. (2007). Vascular pathology of drug-eluting stents.