Role of beta1 and beta2 subunits of the interleukin-12 receptor in determining T helper 1/T helper 2 responses in vivo in the rat

Interleukin-12 (IL-12) responsiveness, and hence capacity to mount a T helper type 1(Th1) immune response, may be regulated via differential expression of the IL-12 receptor beta2 subunit at least in vitro in human and murine cells. To test whether a similar phenomenon operates in vivo in the rat we...

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Bibliographic Details
Published in:Immunology 2000-01, Vol.99 (1), p.109-112
Main Authors: Gillespie, K M, Szeto, C C, Betin, V M, Mathieson, P W
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Autoimmunity
Base Sequence
Gene Expression
Interleukin-12 - metabolism
Mercuric Chloride - pharmacology
Mice
Molecular Sequence Data
Protein Isoforms - genetics
Rats
Rats, Inbred BN
Rats, Inbred Lew
Receptors, Interleukin - genetics
Receptors, Interleukin-12
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Sequence Homology, Nucleic Acid
Spleen - immunology
Th1 Cells - immunology
Th2 Cells - immunology
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Summary:Interleukin-12 (IL-12) responsiveness, and hence capacity to mount a T helper type 1(Th1) immune response, may be regulated via differential expression of the IL-12 receptor beta2 subunit at least in vitro in human and murine cells. To test whether a similar phenomenon operates in vivo in the rat we cloned and sequenced partial cDNAs for rat IL-12Rbeta1 and IL-12Rbeta2 subunits and analysed expression of these genes in vivo in two rat strains with different Th1/Th2 bias. After treatment with mercuric chloride (HgCl2), Brown-Norway rats develop Th2-biased autoimmunity whereas Lewis rats do not develop autoimmunity, instead becoming resistant to Th1-biased diseases to which they are normally susceptible. We report close sequence homology between the segments of the rat IL-12R genes sequenced and corresponding mouse genes (95.6% and 92% for IL-12Rbeta1 and IL-12Rbeta2, respectively). Both Brown-Norway and Lewis rats express both beta1 and beta2 subunits of IL-12 receptor in vivo in spleen; Brown-Norway rats express the beta2 subunit at a lower level than Lewis rats. After HgCl2 treatment, IL-12Rbeta1 expression was not altered but there was down-regulation of IL-12Rbeta2 expression in both strains. We conclude that relative under-expression of IL-12Rbeta2 by Brown-Norway rats contributes to their Th2 bias, and that down-regulation of IL-12Rbeta2 after HgCl2 administration in Lewis rats underlies subsequent resistance to induction of Th1-biased diseases.
ISSN:0019-2805
1365-2567