Abstract 118: Measles Virus Nucleoprotein Induces A Regulatory Immune Response And Reduces Atherosclerosis In Mice
Atherosclerosis, a chronic inflammatory disease of the arterial wall, is promoted by T lymphocyte-mediated immunity. Measles virus nucleoprotein (NP) induces systemic immuno-suppression in murine models by inhibiting antigen-specific T cell proliferation. We hypothesized that a chronic reduction in T cell activation following repetitive administration of NP could inhibit inflammatory response in atherosclerotic process and could prevent plaque development. First, we treated 12 week-old male apoE KO mice with 20 °g of purified recombinant NP intraperitoneally every other week during 3 months. NP treatment led to significant reduction in lesion size (123 628 ± 24 225 °m2 vs 200 894 ± 16 782 °m2, P<0.05). Lesions of mice treated with NP also showed marked 62% reduction in the accumulation of macrophages (P<0.05) , and 70 % reduction of T cells infiltration (P<0.05), indicating reduced plaque inflammation. Second, 30-week old male apoE KO mice were treated as described above during 3 months. We observed a significant 38% reduction (P<0.001) in the size of atherosclerotic lesions in mice treated with NP compared with controls. NP treatment also blocked further macrophage accumulation within the lesions (P<0.05), and significantly enhanced smooth muscle cell content (P<0.05), suggesting a switch toward a stable plaque phenotype. In immunological analysis, CD4+ T cells isolated from spleen of NP-treated animals, using antibodies coupled-magnetic microbeads, proliferated less than those from WT. Furthermore, CD4+ T cell from NP treated mice produced more IL-10 (+30%, P= (−84%, P<0.05), and less IL-4 (−70%, P<0.05) suggesting the induction of a protective regulatory Tr1-like phenotype. In order to demonstrate that the anti-atherosclerotic effects of NP required the induction of a T cell protective immune response, we repeated NP injections in apoE/Rag2 KO mice, deficient in T cells. We found no effect on lesion size in apoE/Rag2 KO mice treated with NP compared with untreated animals. Repetitive administration of measles virus NP to apoE KO mice significantly reduced the development of early atherosclerotic lesions and inhibited the progression of advanced plaques by promoting a IL10-dependent regulatory immune response.