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Published online before print October 4, 2005

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(Journal of Leukocyte Biology. 2005;78:1273-1280.)
© 2005 by Society for Leukocyte Biology

The low-toxicity versions of LPS, MPL® adjuvant and RC529, are efficient adjuvants for CD4⁺ T cells

Bruce S. Thompson^*, Paula M. Chilton^*, Jon R. Ward, Jay T. Evans and Thomas C. Mitchell^*,1

^* Institute for Cellular Therapeutics, Department of Microbiology and Immunology, University of Louisville, Kentucky; and
The Corixa Corporation, Hamilton, Montana

¹ Correspondence: Institute for Cellular Therapeutics, Donald Baxter Research Building, 570 S. Preston Street, Room 404C, Louisville, KY 40202. E-mail: tom.mitchell{at}louisville.edu

Lipopolysaccharide (LPS) has long been known to enhance innate and adaptive immune responses; however, its extreme toxicity precludes its use in clinical settings. The combined toxicity and adjuvanticity of LPS have contributed to the view that immunological adjuvants need to be highly inflammatory to be maximally effective. Here, we compared the effects of LPS with its less-toxic derivatives, monophosphoryl lipid A (MPL) and a chemical mimetic, RC529, on CD4⁺ T cell clonal expansion, long-term survival, and T helper cell type 1 (Th1) differentiation. We found that LPS, MPL, and RC529 had similar effects on CD4⁺ T cell clonal expansion, cell division, and ex vivo survival. Analysis of the ability of activated CD4⁺ T cells to produce interferon- following a 21-day immunization and challenge protocol with LPS and MPL resulted in similar Th1 differentiation. In contrast, we found that LPS was more effective in promoting long-term CD4⁺ T cell responses, as we recovered nearly sixfold more cells following immunization/challenge as compared with treatment with MPL. Our results indicate that low-inflammation adjuvants, such as MPL and RC529, are capable of enhancing short-term CD4⁺ T cell clonal expansion and Th1 differentiation, but inflammatory signaling aids in the long-term retention of antigen-specific T cells.

Key Words: AGP compounds • clonal expansion • T cell survival • mice • Toll-like receptors

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