Stimulating antigen-specific regulatory T cells for an atherosclerosis vaccine

Autor: Benne, N., Jiskoot, W., Kuiper, J., Slutter, B.A.
Rok vydání: 2016
Předmět:
Zdroj: The Journal of Immunology. 196:70.18-70.18
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.196.supp.70.18
Popis: Atherosclerosis is a chronic inflammatory disease of the large and medium sized arteries affecting millions of people world-wide. It is characterised by sub-endothelial retention of low density lipoprotein (LDL), which, over time, leads to the formation of an atherosclerotic plaque. Regulatory T cells (Treg) have been shown to reduce chronic inflammation in atherosclerosis and provide a protective effect. Whereas repeated immunisations with high doses of plaque-specific antigens can induce Treg and reduce the atherosclerotic plaques, particulate formulations may require fewer immunisations and less antigen by specific targeting of the immune system. Therefore, we optimised liposomal formulations to elicit potent Treg responses. Liposomes (average diameter 150–200 nm) consisting of the lipids DSPC, DSPG and cholesterol in different molar ratios were loaded with an ovalbumin-derived CD4+ T cell-specific peptide (OVA323). Murine BMDCs were pulsed with formulations and subsequently cultured with OT-II transgenic CD4+T cells. Compared to free OVA323 or OVA323 mixed with empty liposomes, encapsulation of OVA323 induced increased numbers of Treg as measured by FoxP3 expression. Interestingly, liposomes with the composition 4:1:2 DSPC:DSPG:cholesterol induced the highest Treg responses and also prevented Th1 differentiation as determined by IFN-γ production. Subsequent studies suggest that the 4:1:2 liposomes achieve the optimal balance of antigen loading, flexibility and surface charge to induce Treg. In conclusion, this indicates that liposome composition influences Treg differentiation and liposomes may be used to elicit antigen-specific Treg responses for atherosclerosis vaccination.
Databáze: OpenAIRE
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