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).