Altered Th1/Th2 balance associated with the immunosuppressive/protective effect of the H-2Ab allele on the response to allo-4-hydroxyphenylpyruvate dioxygenase.
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.
Brunner
M
M
Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Larsen
S
S
Sette
A
A
Mitchison
A
A
D015111:4-Hydroxyphenylpyruvate Dioxygenase / Q000276:immunology*; D000483:Alleles; D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D016130:Immunophenotyping; D007165:Immunosuppression Therapy; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D016207:Cytokines; D006183:H-2 Antigens; D012333:RNA, Messenger; D015847:Interleukin-4; D015111:4-Hydroxyphenylpyruvate Dioxygenase