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(Circulation Research. 2007;101:e83.)
© 2007 American Heart Association, Inc.

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Involvement of the CD1d–Natural Killer T Cell Pathway in Neointima Formation After Vascular Injury

Åsa Ström, Maria Wigren, Anna Hultgårdh-Nilsson, Amit Saxena, Maria F. Gomez, Susanna Cardell, Gunilla Nordin Fredrikson, Jan Nilsson

From the Department of Experimental Medicine (A. Ström, A.H.-N., A. Saxena), Lund University; Department of Clinical Sciences (M.W., A. Saxena, M.F.G., G.N.F., J.N.), Malmö University Hospital, Lund University; Department of Microbiology and Immunology (S.C.), Institute of Biomedicine, Göteborg University; and Department of Biomedical Laboratory Science (G.N.F.), Malmö University, Sweden.

Correspondence to Jan Nilsson, Department of Clinical Sciences, Entrance 72;91:12, Malmö University Hospital, 20502 Malmö, Sweden. E-mail jan.nilsson{at}med.lu.se

Recent studies have established that the immune system plays an important role in the development of atherosclerosis. However, its role in regulating the arterial response to mechanical injury is less well studied. Arterial injury is associated with local accumulation of antibodies, and mice lacking functional T and B cells exhibit increased neointima formation, indicating that adaptive immune responses to neoantigens in the damaged tissue modulate the vascular repair process. To study the role of lipid antigen presentation in the arterial response to injury, we analyzed neointima formation in mice deficient in the lipid antigen-presenting molecule CD1d using a carotid collar model. As compared with control mice, neointima formation was reduced by >60% (P<0.01) in CD1d^–/– mice. Moreover, carotid injury of wild-type C57BL/6 mice was associated with expansion of CD1d-restricted natural killer T cells in the spleen and accumulation of natural killer T cells in the periadventitial space of injured arteries. The results suggest that presentation of lipid antigens through the CD1d–natural killer T cell pathway modulates vascular repair responses.

Key Words: arterial injury • antigen presentation • neointima