Reduced Th1 and enhanced Th2 immunity after immunization with Alzheimer's beta-amyloid(1-42).
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).
Town
Terrence
T
Roskamp Institute, University of South Florida, 3515 E. Fletcher Avenue, Tampa, FL 33613, USA. ttown@hsc.usf.edu
Vendrame
Martina
M
Patel
Anant
A
Poetter
Daniel
D
DelleDonne
Anthony
A
Mori
Takashi
T
Smeed
Robert
R
Crawford
Fiona
F
Klein
Thomas
T
Tan
Jun
J
Mullan
Mike
M
D000544:Alzheimer Disease / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000276:immunology*; D000818:Animals; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000145:classification; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016229:Amyloid beta-Peptides; D007074:Immunoglobulin G; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma