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International Immunology, Vol. 15, No. 4, pp. 505-514, April 2003
© 2003 Japanese Society for Immunology

Adjuvant-dependent modulation of Th1 and Th2 responses to immunization with ß-amyloid

David H. Cribbs1, Anahit Ghochikyan2, Vitaly Vasilevko2, Mike Tran1, Irina Petrushina1, Nadya Sadzikava1, Davit Babikyan2, Patrick Kesslak1, Thomas Kieber-Emmons3, Carl W. Cotman1 and Michael G. Agadjanyan2

1 Institute for Brain Aging and Dementia, University of California Irvine, Irvine, CA 92697-4540, USA 2 Department of Immunology, Institute for Molecular Medicine, Huntington Beach, CA 92649, USA 3 Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA

The senior authors (D. H. C. and M. G. A.) contributed equally to this work
Correspondence to: M. G. Agadjanyan; E-mail: magadjanyan{at}immed.org
Transmitting editor: R. Medzhitov

The role of adjuvant on the Th1 and Th2 immune responses to Aß-immunotherapy (Aß42 peptide) was examined in wild-type mice. Fine epitope analysis with overlapping oligomers of the Aß42 sequence identified the 1–15 region as a dominant B cell epitope. The 6–20 peptide was recognized only weakly by antisera from mice administrated with Aß42 peptide formulated in complete Freund’s adjuvant (CFA), alum or TiterMax Gold (TMG). However, mice immunized with Aß42 mixed with QS21 induced a significant antibody response to the 6–20 peptide. The only T cell epitope found was within the 6–28 sequence of Aß42. QS21 and CFA induced the strongest humoral response to Aß, alum was intermediate, and TMG the weakest adjuvant. Analysis of antibody isotypes specific for Aß indicates that alum induces primarily Th2-type immune response, whereas TMG, CFA and QS21 shift the immune responses toward a Th1 phenotype. Stimulation of splenocytes from Aß-immunized mice with Aß40 peptide induced strikingly different cytokine expression profiles. QS21 and CFA induced significant IFN-{gamma}, IL-4 and tumor necrosis factor-{alpha} expression, whereas alum induced primarily IL-4 production. As Th1-type immune responses have been implicated in many autoimmune disorders, whereas Th2-type responses have been shown to inhibit autoimmune disease, the choice of adjuvant may be critical for the design of a safe and effective immunotherapy for Alzheimer’s disease.

Keywords: antibody, B/T cell response, cytokine, epitope, peptide


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