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Role of β 1 and β 2 subunits of the interleukin‐12 receptor in determining T helper 1/T helper 2 responses in vivo in the rat
Author(s) -
Gillespie K. M.,
Szeto C.C.,
Betin V. M.,
Mathieson P. W.
Publication year - 2000
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2000.00927.x
Subject(s) - biology , in vivo , protein subunit , autoimmunity , gene , receptor , immune system , gene expression , microbiology and biotechnology , ex vivo , interleukin 10 receptor, alpha subunit , immunology , g alpha subunit , genetics
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 β 2 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‐12Rβ 1 and IL‐12Rβ 2 subunits and analysed expression of these genes in vivo in two rat strains with different Th1/Th2 bias. After treatment with mercuric chloride (HgCl 2 ), 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‐12Rβ 1 and IL‐12Rβ 2 , respectively). Both Brown–Norway and Lewis rats express both β 1 and β 2 subunits of IL‐12 receptor in vivo in spleen; Brown–Norway rats express the β 2 subunit at a lower level than Lewis rats. After HgCl 2 treatment, IL‐12Rβ 1 expression was not altered but there was down‐regulation of IL‐12Rβ 2 expression in both strains. We conclude that relative under‐expression of IL‐12Rβ 2 by Brown–Norway rats contributes to their Th2 bias, and that down‐regulation of IL‐12Rβ 2 after HgCl 2 administration in Lewis rats underlies subsequent resistance to induction of Th1‐biased diseases.