FUNCTIONAL CD40 LIGAND EXPRESSION ON T-LYMPHOCYTES IN THE ABSENCE OF T-CELL RECEPTOR ENGAGEMENT - INVOLVEMENT IN INTERLEUKIN-2-INDUCED INTERLEUKIN-12 AND INTERFERON-GAMMA PRODUCTION

Despite the fact that the great majority of T cells at the site of an inflammatory response are not antigen specific, the mechanisms leading to activation and recruitment of these bystander T cells are poorly u nderstood. We previously reported that soluble (s)CD23 potentiated the interleukin (IL)-2-induced interferon (IFN)-gamma production by T cel ls co-cultured with autologous monocytes in the absence of T cell rece ptor (TCR) engagement. Our present data demonstrate that the IL-2-indu ced IFN-gamma secretion, in the presence but also in the absence of sC D23, is strictly IL-12 dependent, inasmuch as anti-IL-12 antibody abro gated both responses. Most interestingly, anti-CD40 ligand (CD40L) mon oclonal antibody significantly inhibited IL-2-induced IL-12 as well as IFN-gamma production. These results suggest that CD40L was expressed on T cells in the absence of TCR engagement. Indeed, purified unstimul ated T cells readily expressed CD40L. IL-2 and monocytes did not up-re gulate CD40L on resting T cells. It is proposed that low levels of CD4 0L expression on non-antigen stimulated T cells are sufficient to sign al through CD40 molecules on accessory cells and to induce IL-12 secre tion, which in turn can synergize with IL-2 for the induction of IFN-g amma production, thus contributing to the inflammatory process.