CD8 ⁺ T Lymphocytes Regulate the Arteriogenic Response to Ischemia by Infiltrating the Site of Collateral Vessel Development and Recruiting CD4 ⁺ Mononuclear Cells Through the Expression of Interleukin-16

Abstract

Background-Previous studies have demonstrated that macrophages and CD4ϩ T lymphocytes play pivotal roles in collateral development. Indirect evidence suggests that CD8 ϩ T cells also play a role. Ϫ/Ϫ mice immediately after femoral artery ligation, they selectively homed to the ischemic hind limb but were unable to recruit CD4 ϩ mononuclear cells and did not improve blood flow recovery. Conclusions-These results demonstrate that CD8ϩ T cells importantly contribute to the early phase of collateral development. After femoral artery ligation, CD8 ϩ T cells infiltrate the site of collateral vessel growth and recruit CD4 ϩ mononuclear cells through the expression of IL-16. Our study provides further evidence of the significant role of the immune system in modulating collateral development in response to peripheral ischemia. (Circulation. 2006;113:118-124.)

Ischemia leads to delayed union during fracture healing: A mouse model

“…Femoral artery ligation creates a severe ischemic environment in the hind limbs, 4,14 and our data show that blood supply to the fracture site did not recover until 14 days post-injury. This acute, persistent ischemia led to multiple defects in fracture repair.…”

“…In this model, blood flow drops precipitously and then returns through the formation of collateral blood vessels over the next 4 weeks. 4 The effect of ischemia on cell proliferation, death, and differentiation, and production of cartilage and bone matrix in nonstabilized fractures were then assessed.…”

Surgical Stress-Induced Immune Cell Redistribution Profiles Predict Short-Term and Long-Term Postsurgical Recovery

“…State-dependent differences in relative concentrations of stress hormones (principally epinephrine, norepinephrine, and cortisol) released during surgery are also likely to be important as it has been shown that stress-induced changes in leukocyte distribution are mediated by glucocorticoid and catecholamine hormones 13,19,35,40 . Although neutrophils and monocytes/macrophages play a prominent role during early stages of wound-healing, lymphocytes are involved in later stages, regulate postoperative healing and angiogenesis, and are thought to be critical for effective and optimized wound-healing [41][42][43][44][45][46][47] . Our data suggest that lymphocyte redistribution profiles during surgery are significant predictors of recovery.…”

Modeling Risk Factors and Confounding Effects in Stroke

“…Does postischemic inflammation involve similar mechanisms and/or effects in the periphery and in the brain? Although several reports showed that oxidative stress and recruitment of inflammatory cells are harmful mainly in stroke, superoxide-initiated inflammation and monocyte recruitment seem crucial for peripheral, flow-or ischemia mediated vascular remodeling (156,157). May modest and well-controlled inflammation facilitate processes of repair?…”