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Lipid Vesicle Size Determines the Th1 or Th2 Response to Entrapped Antigen¹

James M. Brewer^2,*,§, Laurence Tetley, James Richmond, Foo Y. Liew^§ and James Alexander^*

^* Department of Immunology, University of Strathclyde, Glasgow, Scotland; Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, Scotland; Department of Pathology, Glasgow Royal Infirmary, Glasgow, Scotland; and ^§ Department of Immunology, University of Glasgow, Western Infirmary, Glasgow, Scotland

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 225 nm preferentially induces Th1 responses, as characterized by increased titers of IgG2a in plasma and elevated IFN- production by lymph node cells. However, preparation of the same quantity of Ag in vesicles with mean diameter of 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 (225 nm) vesicles could induce IL-12 production, smaller vesicles (155 nm) could not. However, small vesicles did induce higher levels of IL-1ß 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- 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.

This article has been cited by other articles:

				J. M. Brewer, K. G. J. Pollock, L. Tetley, and D. G. Russell Vesicle Size Influences the Trafficking, Processing, and Presentation of Antigens in Lipid Vesicles J. Immunol., November 15, 2004; 173(10): 6143 - 6150. [Abstract] [Full Text] [PDF]