C-REL IS A TARGET OF PENTOXIFYLLINE-MEDIATED INHIBITION OF T-LYMPHOCYTE ACTIVATION

The possible clinical use of the methyl xanthine derivative, pentoxify lline (PF), for the treatment of T cell-dependent diseases is being no ted with increasing interest. In this paper, we studied the molecular consequences of PF treatment during lymphocyte activation. We found th at in T cells, anti-CD3-induced c-Rel expression was blocked by PF, wh ereas the induction of other NF-kappa B family members was not signifi cantly affected. However, induction of NF-AT, which has the same signa ling requirements as c-Rel induction, was not inhibited by PF. Among g enes that respond to these transcription factors, IL-2 mRNA induction was suppressed by PF, whereas IL-2R alpha chain mRNA induction was not affected. These observations implicated c-Rel as an IL-2 promoter fac tor, for which experimental support was obtained from transient transf ection experiments. In contrast with the observation in T cells, c-Rel induction was not blocked by PF in B cells. The greater selectivity o f PF, compared with FK506, at both the molecular and cellular levels m ay prove advantageous in manipulating T cell responses in vivo.