Involvement of the CD27-CD70 co-stimulatory pathway in allogeneic T-cell response to follicular lymphoma cells

Non-activated follicular lymphoma (FL) cells do not function as effective a ntigen-presenting cells ill vivo. CD40 activation of FL cells up-regulates critical adhesion and co-stimulatory molecules, thereby inducing lymphoma-s pecific cytotoxic T cells in vitro. However, other evidence suggests that C D70 is another important co-stimulatory molecule involved in antigen depend ent T-cell activation. Here, we showed that freshly isolated FL cells from eight diagnostic biopsies expressed intermediate to high levels of CD27, wh ereas only insignificant levels of CD70 were detected on their cell surface . Together with the low to intermediate expression of B7, these findings he lp to explain the poor antigen-presenting capacity of non-activated FL cell s, Activation of FL cells by CD27 and CD40 induced a significantly higher a lloantigen T-cell response than CD40 alone, whereas CD27 activation induced only a mostly insignificant T-cell proliferation, Both CD40 and CD27+ CD40 activation resulted in a high up-regulation of CD70 and B7 molecules, wher eas CD27 activation up-regulated CD70 but not B7 expression on the surface of FL cells, Thus, expression of both CD70 and B7 co-stimulatory molecules appears to be essential for an efficient T-cell-mediated immune response, H owever, the molecules responsible for the significantly higher alloantigen T-cell response to FL cells activated through CD27 and CD40 remain to be id entified. Ln summary, we conclude that CD27+CD70 represents another co-stim ulatory pathway involved in T-cell-mediated immune responses to FL cells, O ur findings suggest that several costimulatory pathways exist and should be taken into consideration to optimize antigen presentation for the generati on of lymphoma-directed cytoloxic T cells for for cells adoptive immunother apy.