title: Enhanced neointima formation following arterial injury in immune deficient Rag-1-/- mice is attenuated by adoptive transfer of CD8 T cells.
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(+)CD44(hi) and CD8(+)CD44(hi) 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.
authors.affiliation: Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Los Angeles, California, United States of America. DimayugaP@cshs.org
authors.forename: Paul C
authors.initials: PC
authors.lastname: Dimayuga
authors.forename: Kuang-Yuh
authors.initials: KY
authors.lastname: Chyu
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kirzner
authors.forename: Juliana
authors.initials: J
authors.lastname: Yano
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhao
authors.forename: Jianchang
authors.initials: J
authors.lastname: Zhou
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
authors.forename: Bojan
authors.initials: B
authors.lastname: Cercek
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002339:Carotid Arteries / Q000473:pathology*; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D058426:Neointima / Q000276:immunology*
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein