Lipid Vesicle Size Determines the Th1 or Th2 Response to Entrapped Antigen

Understanding the factors that control the differential induction of Th1 and Th2 responses is a key immunologic objective with profound implications for vaccination and immunotherapy of infectious and autoimmune diseases. Using Ag formulated in lipid vesicles prepared from nonionic surfactants, we d...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-10, Vol.161 (8), p.4000-4007
Main Authors: Brewer, James M, Tetley, Laurence, Richmond, James, Liew, Foo Y, Alexander, James
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Antigens - chemistry
Antigens - immunology
Antigens - ultrastructure
Immunity, Cellular
Immunoglobulin G - immunology
Lipids - chemistry
Lipids - immunology
Membranes, Artificial
Mice
Mice, Inbred BALB C
Microscopy, Electron
T-Lymphocyte Subsets - immunology
Th1 Cells - immunology
Th2 Cells - immunology
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Summary:Understanding the factors that control the differential induction of Th1 and Th2 responses is a key immunologic objective with profound implications for vaccination and immunotherapy of infectious and autoimmune diseases. Using Ag formulated in lipid vesicles prepared from nonionic surfactants, we describe a novel mechanism influencing the balance of the Th1 or Th2 response. Our results indicate that inoculation of BALB/c mice with vesicles with a mean diameter > or = 225 nm preferentially induces Th1 responses, as characterized by increased titers of IgG2a in plasma and elevated IFN-gamma production by lymph node cells. However, preparation of the same quantity of Ag in vesicles with mean diameter of < or = 155 nm induces a Th2 response, as identified by IgG1 in the absence of IgG2a production and increased lymph node IL-5 production. Although large (> or = 225 nm) vesicles could induce IL-12 production, smaller vesicles (< or = 155 nm) could not. However, small vesicles did induce higher levels of IL-1beta production by macrophages than larger vesicles. The role of IL-12 in this response was confirmed in IL-12-deficient mice, whose spleen cells failed to produce IFN-gamma following in vivo priming with Ag prepared in large vesicles. Our results therefore indicate that macrophages respond to endocytosis of large or small vesicles by producing different patterns of cytokines that can subsequently direct the immune response toward a Th1 or a Th2 phenotype.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.161.8.4000