Role of β1 and β2 subunits of the interleukin-12 receptor in determining T helper 1/T helper 2 responses in vivo in the rat

Abstract

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 β2 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-12Rβ1 and IL-12Rβ2 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 IL12R genes sequenced and corresponding mouse genes (95-6% and 92% for IL-12Rβ1 and IL-12Rβ2, respectively). Both Brown-Norway and Lewis rats express both β1 and β2 subunits of IL-12 receptor in vivo in spleen; Brown-Norway rats express the β2 subunit at a lower level than Lewis rats. After HgCl2 treatment, IL-12Rβ1 expression was not altered but there was down-regulation of IL-12Rβ2 expression in both strains. We conclude that relative under-expression of IL-12Rβ2 by Brown-Norway rats contributes to their Th2 bias, and that down-regulation of IL-12Rβ2 after HgCl2 administration in Lewis rats underlies subsequent resistance to induction of Th1-biased diseases.