Reduced Th1 and enhanced Th2 immunity after immunization with Alzheimer's beta-amyloid(1-42).
J Neuroimmunol
; 132(1-2): 49-59, 2002 Nov.
Article
em En
| MEDLINE
| ID: mdl-12417433
ABSTRACT
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).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Peptídeos beta-Amiloides
/
Células Th2
/
Células Th1
/
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article