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Natural killer cells and CD4+ T-cells modulate collateral artery development

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Author: Weel, V. van · Toes, R.E.M. · Seghers, L. · Deckers, M.M.L. · Vries, M.R. de · Eilers, P.H. · Sipkens, J. · Schepers, A. · Eefting, D. · Hinsbergh, V.W.M. van · Bockel, J.H. van · Quax, P.H.A.
Type:article
Date:2007
Institution: TNO Kwaliteit van Leven
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 11, 27, 2310-2318
Identifier: 240272
doi: doi:10.1161/ATVBAHA.107.151407
Keywords: Biomedical Research · Angiogenesis · Animal models of human disease · Peripheral vascular disease · biological marker · CD3 antigen · CD4 antigen · vascularization · Animals · Arterial Occlusive Diseases · CD4-Positive T-Lymphocytes · Collateral Circulation · Disease Models, Animal · Femoral Artery · Hindlimb · Ischemia · Killer Cells, Natural · Mice · Mice, Inbred BALB C · Mice, Knockout · Neovascularization, Physiologic

Abstract

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.