Reduced Th1 and enhanced Th2 immunity after immunization with Alzheimer's beta-amyloid(1-42)

• Published in: Journal of neuroimmunology 2002-11, Vol.132 (1-2), p.49-59
• Main Authors: Town, Terrence, Vendrame, Martina, Patel, Anant, Poetter, Daniel, DelleDonne, Anthony, Mori, Takashi, Smeed, Robert, Crawford, Fiona, Klein, Thomas, Tan, Jun, Mullan, Mike
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - therapy; Amyloid beta-Peptides - immunology; Animals; Female; Immunization; Immunoglobulin G - classification; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-4 - biosynthesis; Mice; Mice, Inbred C57BL; Mice, Transgenic; Peptide Fragments - immunology; Th1 Cells - immunology; Th2 Cells - immunology
• ISSN: 0165-5728
• DOI: 10.1016/S0165-5728(02)00307-7

It has been demonstrated that immunization of transgenic mouse models of Alzheimer's disease (AD) with amyloid-beta(1-42) peptide (Abeta(1-42)) results in prevention of Abeta plaque formation and amelioration of established plaques in the brain. As the response of the T lymphocyte helper (Th) arm of the immune response had not yet been investigated after Abeta immunization, we i.p. immunized C57BL/6 mice with Abeta(1-42), Abeta(1-40), or phosphate-buffered saline (PBS), and examined markers of Th1 and Th2 immune responses in spleen and in splenocytes from these mice. Spleens from Abeta(1-42)-immunized mice demonstrated decreased interleukin-12 receptor beta chain expression compared to mice immunized with Abeta(1-40) or PBS. Consistently, following stimulation with concanavalin A or anti-CD3 antibody, primary splenocytes from Abeta(1-42)-immunized mice demonstrated elevated secretion of interleukin-4 and interleukin-10, and decreased levels of interferon-gamma. To validate this Th1-->Th2 shift in a transgenic mouse model of AD, we immunized Tg APP(sw) mice (line 2576) with Abeta(1-42) and found decreased Th1 (interleukin-2 and interferon-gamma) and elevated Th2 (interleukin-4 and interleukin-10) cytokines in their stimulated primary splenocytes. Interferon-gamma was markedly reduced and interleukin-10 was increased in blood plasma from these mice, effects that were associated with dramatically mitigated Abeta deposition after Abeta(1-42) immunization. Taken together, these results show enhanced Th2 and down-regulated Th1 immunity following immune challenge with Abeta(1-42).