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


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 J alpha281-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.
van Weel
V
V
Gaubius Laboratory, TNO-QOL, P.O. Box 2215, 2301CE Leiden, The Netherlands.
Toes
R E M
RE
Seghers
L
L
Deckers
M M L
MM
de Vries
M R
MR
Eilers
P H
PH
Sipkens
J
J
Schepers
A
A
Eefting
D
D
van Hinsbergh
V W M
VW
van Bockel
J H
JH
Quax
P H A
PH
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000276:immunology* / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D003097:Collateral Circulation / Q000276:immunology*; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000254:growth & development; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000276:immunology*