Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 195, Issue 5, Pages 617-624Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20011889
Keywords
alpha-galactosylceramide; NKT cells; adjuvant; malaria vaccines; CD8(+) T cells
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Funding
- NCI NIH HHS [CA-52511, R01 CA052511] Funding Source: Medline
- NIAID NIH HHS [AI-47840, AI-01682, AI-40656, AI-33314] Funding Source: Medline
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The important role played by CD8(+) T lymphocytes in the control of parasitic and viral infections, as well as tumor development, has raised the need for the development of adjuvants capable of enhancing cell-mediated immunity. It is well established that protective immunity against liver stages of malaria parasites is primarily mediated by CD8(+) T cells in mice. Activation of natural killer T (NKT) cells by the glycolipid ligand, alpha-galactosylceramide (alpha-GalCer), causes bystander activation of NK, B, CD4(+), and CD8(+) T cells. Our study shows that coadininistration of alpha-GalCer with suboptimal doses of irradiated sporozoites or recombinant viruses expressing a malaria antigen greatly enhances the level of protective anti-malaria immunity in mice. We also show that coadministration of alpha-GalCer with various different immunogens strongly enhances antigen-specific CD8(+) T cell responses, and to a lesser degree, Th1-type responses. The adjuvant effects of alpha-GalCer require CD1d molecules, Valpha14 NKT cells, and interferon gamma. As alpha-GalCer stimulates both human and murine NKT cells, these findings should contribute to the design of more effective vaccines against malaria and other intracellular pathogens, as well as tumors.
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