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M9650197.TXT
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1996-03-09
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Document 0197
DOCN M9650197
TI Altered Th1/Th2 balance associated with the immunosuppressive/protective
effect of the H-2Ab allele on the response to
allo-4-hydroxyphenylpyruvate dioxygenase.
DT 9605
AU Brunner M; Larsen S; Sette A; Mitchison A; Deutsches
Rheuma-Forschungszentrum, Berlin, Germany.
SO Eur J Immunol. 1995 Dec;25(12):3285-9. Unique Identifier : AIDSLINE
MED/96140664
AB The H-2Ab allele exerts a dominant down-regulatory effect on the
anti-allo-HPPD (4-hydroxyphenylpyruvate dioxygenase) antibody response,
through a hitherto unknown mechanism. In the present study, the
allo-variable peptide bound to responder H-2Ak molecules with higher
affinity than to H-2Ab ones, arguing against the operation of an
affinity hierarchy. Quantitative polymerase chain reaction revealed
differences in cytokine mRNA expression between suppressed and
high-responder mice. Lymph node cells of responder but not suppressed
mice contained high levels of interleukin (IL)-4 mRNA as early as 11 h
post-immunization and continued to do so for at least 8 days; this early
burst was paralleled by a small burst in transforming growth factor
(TGF)-beta mRNA level. Differences in IL-12 mRNA were not detected,
although an early IL-12 effect could not be excluded. Interferon
(IFN)-gamma appeared to contribute to the suppression at later time
points. Early treatment of responder mice with anti-IL-4 monoclonal
antibody (11B11) down-regulated the antibody response. The proliferative
T cell response from hyperimmunized mice was reduced but still
detectable in the presence of an H-2Ab allele. Thus, in the presence of
this allele, the Th1 response is enhanced and that of Th2 cells
suppressed, apparently as a result of the bias of H-2Ab-restricted T
cells in favor of the Th1 subset.
DE *Alleles Animal *Antibody Formation Base Sequence
Cytokines/BIOSYNTHESIS Female H-2 Antigens/GENETICS/*IMMUNOLOGY
Immunophenotyping *Immunosuppression Interleukin-4/IMMUNOLOGY Mice
Mice, Inbred CBA Molecular Sequence Data Protein Binding/IMMUNOLOGY
RNA, Messenger/BIOSYNTHESIS Support, Non-U.S. Gov't Th1
Cells/*IMMUNOLOGY Th2 Cells/*IMMUNOLOGY 4-Hydroxyphenylpyruvate
Dioxygenase/*IMMUNOLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).