title: Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice.
abstract: BACKGROUND
  T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model.
  
  
  RESULTS
  One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved.
  
  
  CONCLUSIONS
  These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.
authors.affiliation: Laboratory of Vascular Biology, Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Suite 4B 1, 110 Irving Street, NW, Washington, DC 20010, USA. geko50@hotmail.com
authors.forename: Eugenio
authors.initials: E
authors.lastname: Stabile
authors.forename: Mary Susan
authors.initials: MS
authors.lastname: Burnett
authors.forename: Craig
authors.initials: C
authors.lastname: Watkins
authors.forename: Timothy
authors.initials: T
authors.lastname: Kinnaird
authors.forename: Alessia
authors.initials: A
authors.lastname: Bachis
authors.forename: Andrea
authors.initials: A
authors.lastname: la Sala
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Miller
authors.forename: Matie
authors.initials: M
authors.lastname: Shou
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Epstein
authors.forename: Shmuel
authors.initials: S
authors.lastname: Fuchs
mesh_terms: D000208:Acute Disease; D000818:Animals; D001158:Arteries / Q000473:pathology / Q000503:physiopathology*; D015704:CD4 Antigens / Q000235:genetics* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology / Q000637:transplantation; D002478:Cells, Cultured; D003097:Collateral Circulation / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D005263:Femoral Artery / Q000503:physiopathology; D005434:Flow Cytometry; D006614:Hindlimb / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D007249:Inflammation / Q000473:pathology; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000276:immunology; D020127:Recovery of Function; D012039:Regional Blood Flow
chemical_list: D015704:CD4 Antigens