Identification of RANTES as a novel immunomodulator of the maternal allogeneic response

We investigated the immunomodulatory role of chemokines in the maternal allogeneic T-cell response. In comparison with fertile women, we found in patients with recurrent spontaneous abortions (RSA), a significant decreased sera level of RANTES that increased after immunization with paternal leukocytes. Since blocking factors with unknown identity are detected in sera from fertile women, we hypothesized that RANTES might function as a novel blocking factor and therefore we explored its cell growth inhibitory properties during the allogenic T-cell response. We demonstrated that RANTES inhibits the mixed lymphocyte reaction (MLR) in a dose-dependent manner. Investigation of the mechanisms involved in cell growth inhibition revealed that this beta-chemokine induces T-cell apoptosis through modulation of Bcl-2 protein levels and by a caspase-independent mechanism and does not involve modulation of Fas (CD95) antigen expression. Our results provides experimental evidence implicating RANTES as a suppressor of alloantigen specific T-cell responses and indicates that this beta-chemokine might function as a novel blocking factor and reliable marker for successful allotreatment of RSA patients.