Mechanism for maintenance of dominant T helper 1 immune responses in Lewisrats

Lewis rats are prone to T helper (Th) I immune responses, whereas Brown Nor way (BN) rats are susceptible to Th2 immune responses. Yet, the precise mec hanism of induction of the different outcome between these two strains rema ined elusive. We investigated the expression levels of some cytokines, thei r receptors and accessory molecules responsible for the polarization of ant igen-specific immune response into a predominant Th1 or Th2 profile in Lewi s and BN rats. Lymph node (LN) cells collected from rats immunized with sho rt ragweed ((RW) were used directly or after stimulation in vitro with RW f or 3 days. Expression of cytokines, their receptors and accessory molecules in these LN cells were tested by reverse transcriptase-PCR. Culture supern atant was used for ELISA to detect IL-12 protein. We observed clear differe nces between these strains in the expression of IL-12p40, which was high in LN cells of Le sis rats even before stimulation in vitro. In addition, a h igher amount of IL-12 was present in the culture supernatant in Lewis rats. Upregulation of the expression of IL-12 receptor beta1, beta2, IFN-gamma r eceptor alpha and beta genes were more prominent in I,e,ris rats rather tha n BN rats. Furthermore, attenuated expression of CD40 and CD40 ligand by st imulation in vitro was noted only in BN rats. Changes in expression of thes e molecules by stimulation as well as higher basal level of IL-12p40 might have led to the activation of Th1 cells in Lewis rats.