Natural killer cells and CD4+ T-cells modulate collateral artery development
article
OBJECTIVE - The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. METHODS AND RESULTS - Lymphocytes, detected with markers for NK1.1, CD3, and CD4, invaded the collateral vessel wall. Arteriogenesis was impaired in C57BL/6 mice depleted for Natural Killer (NK)-cells by anti-NK1.1 antibodies and in NK-cell-deficient transgenic mice. Arteriogenesis was, however, unaffected in Jα281-knockout mice that lack NK1.1 Natural Killer T (NKT)-cells, indicating that NK-cells, rather than NKT-cells, are involved in arteriogenesis. Furthermore, arteriogenesis was impaired in C57BL/6 mice depleted for CD4 T-lymphocytes by anti-CD4 antibodies, and in major histocompatibility complex (MHC)-class-II-deficient mice that more selectively lack mature peripheral CD4 T-lymphocytes. This impairment was even more profound in anti-NK1.1-treated MHC-class-II-deficient mice that lack both NK- and CD4 T-lymphocytes. Finally, collateral growth was severely reduced in BALB/c as compared with C57BL/6 mice, 2 strains with different bias in immune responsiveness. CONCLUSIONS - These data show that both NK-cells and CD4 T-cells modulate arteriogenesis. Promoting lymphocyte activation may represent a promising method to treat ischemic disease. © 2007 American Heart Association, Inc.
Topics
Biomedical ResearchAngiogenesisAnimal models of human diseasePeripheral vascular diseasebiological markerCD3 antigenCD4 antigenvascularizationAnimalsArterial Occlusive DiseasesCD4-Positive T-LymphocytesCollateral CirculationDisease Models, AnimalFemoral ArteryHindlimbIschemiaKiller Cells, NaturalMiceMice, Inbred BALB CMice, KnockoutNeovascularization, Physiologic
TNO Identifier
240272
ISSN
10795642
Source
Arteriosclerosis, Thrombosis, and Vascular Biology, 27(11), pp. 2310-2318.
Pages
2310-2318
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