TY - JOUR
T1 - Natural killer cells and CD4+ T-cells modulate collateral artery development
AU - Van Weel, V.
AU - Toes, R. E.M.
AU - Seghers, L.
AU - Deckers, M. M.L.
AU - De Vries, M. R.
AU - Eilers, P. H.
AU - Sipkens, J.
AU - Schepers, A.
AU - Eefting, D.
AU - Van Hinsbergh, V. W.M.
AU - Van Bockel, J. H.
AU - Quax, P. H.A.
PY - 2007/11/1
Y1 - 2007/11/1
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Animal models of human disease
KW - Peripheral vascular disease
UR - http://www.scopus.com/inward/record.url?scp=36049012324&partnerID=8YFLogxK
U2 - 10.1161/ATVBAHA.107.151407
DO - 10.1161/ATVBAHA.107.151407
M3 - Article
C2 - 17717295
AN - SCOPUS:36049012324
VL - 27
SP - 2310
EP - 2318
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 11
ER -