Role of beta(1) and beta(2) 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 help er type 1(Th1) immune response, may be regulated via differential expressio n of the IL-12 receptor beta(2) subunit at least in vitro in human and muri ne cells. To test whether a similar phenomenon operates in vivo in the rat we cloned and sequenced partial cDNAs for rat IL-12R beta(1) and IL-12R bet a(2) subunits and analysed expression of these genes in vivo in two rat str ains with different Th1/Th2 bias. After treatment with mercuric chloride (H gCl2), Brown-Norway rats develop Th2-biased autoimmunity whereas Lewis rats do not develop autoimmunity, instead becoming resistant to Th1-biased dise ases to which they are normally susceptible. We report close sequence homol ogy between the segments of the rat IL-12R genes sequenced and correspondin g mouse genes (95.6% and 92% for IL-12R beta(1) and IL-12R beta(2), respect ively). Both Brown-Norway and Lewis rats express both Pi and beta(2) subuni ts of IL-12 receptor in vivo in spleen; Brown-Norway rats express the beta( 2) subunit at a lower level than Lewis rats. After HgCl2 treatment, IL-12R beta(1) expression was not altered but there was down-regulation of IL-12R beta(2) expression in both strains. We conclude that relative under-express ion of IL-12R beta(2) by Brown-Norway rats contributes to their Th2 bias, a nd that down-regulation of IL-12R beta(2) after HgCl2 administration in Lew is rats underlies subsequent resistance to induction of Th1-biased diseases .